Dr. Mark Jay Shlomchik |
|
Yale University School of Medicine Laboratory Medicine Blood Bank Associate DirectorAppointed: 1993 Yale University School of Medicine Laboratory Medicine and Immunobiology Professor |  |
Mailing Address333 Cedar Street Yale University TAC S541A Box 208035 New Haven, Connecticut 06520-8035United States | Contact InformationPhone: (203) 737-2089 Fax: (203) 785-5415 mark.shlomchik@yale.edu http://info.med.yale.edu/immuno/fac_shlomchik.html |
Qualifications
M.D., Fox Chase Cancer Center and Hospital of University of Pennsylvania, 1989.
Ph.D., Fox Chase Cancer Center and Hospital of University of Pennsylvania, 1989.
B.A., Fox Chase Cancer Center and Hospital of University of Pennsylvania, 1981.
Fellowship, Fox Chase Cancer Center and Hospital of University of Pennsylvania.
Expertise and Research Interests
The long-term interests of our lab include the regulation of autoreactive B lymphocytes and the development of high affinity B cell immune responses and memory cells. More recently, we have also developed an interest in the mechanisms by which T cells are activated in Graft vs. Host Disease (GVHD) and the subsets of T cells that are pathogenic. We have emphasized in vivo models in all the work.
To study the regulation of autoreactive B cells in normal mice and the loss of regulation in autoimmune-prone animals, we have used transgenic (Tg) mouse models to ask how B cells which express a disease-related autoantibody, Rheumatoid Factor (RF), are prevented from causing harm in normal mice. We first demonstrated that these cells develop, mature and are immunocompetent in non-autoimmune mice (Hannum et al., 1996). Recent results demonstrate that these Tg RF B cells are spontaneously activated in autoimmune-prone mice, but only when the autoantigen is present (Wang and Shlomchik, 1999). We have recently used this system to develop a method to visualize the initiating events of B cell autoimmunity (William et al., 2005a; William et al., 2005b), an elusive goal. We expect this to be a powerful new model system for understanding of the origins of autoimmunity. For example, we have recently found that the early and perhaps chronic events in the MRL.Faslpr lupus model are not taking place in the germinal center (GC) as originally thought, but instead involve continuous proliferation at the outer edge of the T cell zone, where T and B cells normally interact only transiently (William et al., 2002). Quite surprisingly, we have shown that very active somatic hypermutation of Ig V regions is taking place at this site, thus dissociating mutation from the GC environment for the first time and also raising the possibility that mutation outside of GCs can lead to loss of self-tolerance (William et al., 2002). Interestingly, we found that autoreactive B cells on a normal BALB/c background still entered GCs and began to mutate there, but never made autoantibodies, thus suggesting a new self-tolerance checkpoint. We are actively investigating how autoreactive B cells become activated at extrafollicular sites, using a new method that we discovered to induce it (rather than wait for it to happen spontaneously) as well as a cell transfer system. These techniques greatly improve our ability to dissect the mechanisms. We are currently investigating the roles of TLRs, DCs, T cells, BAFF/APRIL family members and other costimulatory molecules using a combination of knockout mice and inhibitors. We also recently developed a BCR knockin version of the AM14 mouse, which undergoes isotype switch. This facilitates our identification of activated cells, the study of switch regulation, and also the development of memory.
An emerging interest in this area is the role of Toll-like receptors in activating autoreactive B cells (Leadbetter et al., 2002, Vigliante et al., 2003, Christensen, et al., submitted, 2005). These studies, partly in collaboration with Dr. Marshak-Rothstein at Boston University, have provided significant new insights into how self-Ags stimulate the immune system in autoimmunity by stimulating TLRs. In two recent studies, we have shown how this explains the generation of the two major types of lupus-related autoantibodies, anti-DNA and anti-RNA. Using knockout mice, we showed that the former is controlled by TLR9 and the latter by TLR7. Surprisingly though, we found that while deletion of TLR7 ameliorated disease, deletion of TLR9 exacerbated it; thus, only TLR7 appears to be a good therapeutic target (Christensen et al., 2005; Christensen et al., 2006). We are currently investigating the mechanism by which TLR9 normally regulates disease, as well as the cell types that need to express both TLRs to promote disease.
An important related focus has been on how activated autoreactive B cells contribute to pathogenesis in systemic autoimmunity. Traditionally B cells have been thought of mainly as sources of pathogenic autoantibody. We challenged this view with the notion that a main function of B cells is to activate autoreactive, pathogenic T cells, in an antigen-specific way. First, we deleted B cells from autoreactive mice and showed that T cell activation and disease was ablated (Chan and Shlomchik, 1998; Shlomchik et al., 1994). Second, we created a novel mouse model which had B cells expressing only the membrane form of IgM and that could not secrete Ab (Chan et al., 1999). In the autoimmune-prone mouse, such B cells promoted both T cell activation and disease. We have recently developed a Tg mouse that expresses human CD20 on all B cells and can be used to deplete B cells with anti-CD20 at any time. Using this model, we recently found that depletion of B cells in adult autoimmune-prone mice can indeed ameliorate disease, but at the same time we discovered that depleting B cells in the midst of autoimmunity is markedly more difficult than in normal strains, thus revealing an unexpected therapeutic barrier (Ahuja, et al, submitted). We are now working on why this is the case.
The second major interest in B cell biology is the development of high affinity B cell immune responses and memory. We are using a Tg mouse model which has B cells that cannot secrete antibody to explore whether antigen retained as immune complexes on follicular dendritic cells (FDCs) is necessary for the development and maintenance of memory B cells. B cells in these mice make normal primary and secondary immune responses including germinal centers and somatic mutation (Hannum et al., 2000). We have also recently found that normal memory B cells form in these animals survive without further cell division for months after their initial development (Anderson et al., 2006b). Thus, immune complexes on FDCs are not necessary for these processes. We are now investigating the identity and functional capacity of the memory cells formed and have used microarray expression profiling to identify a host of genes differentially expressed between naïve and memory B cells. Many of these have been confirmed at the protein level, providing new insights into the functions of memory B cells. We are currently using knockout mice to test the roles of some of these molecules in memory development and function in vivo We also have a program to study the dynamics of germinal center B cells using both experimental and computer modeling approaches, as well as in vivo multiphoton microscopy, a program led by Associate Research Scientist Dr. Ann Haberman (Hauser, et al., submitted).
Over the past several years we have developed an interest in the immunopathology surrounding stem cell transplantation We have focused on chronic GVHD (cGVHD), applying modern genetics and molecular techniques to a murine model. We have already shown (surprisingly) that host-derived antigen-presenting cells are not required to induce cGVHD. Further, we have found that host-derived CD4+/CD25+ T cells play an important role in regulating cGVHD (Anderson et al., 2005; Anderson et al., 2004). Most recently, in collaboration with Dr. Warren Shlomchik, we found that donor memory T cells do not cause GVHD, although they engraft and function (Anderson et al., 2003). This could represent a major therapeutic approach to minimize GVHD while preserving GVL and immunocompetence in recipients. We are currently investigating the reasons why memory T cells do not cause GVHD.
If you are interested in working on or discussing any of these areas, feel free to contact me anytime.
To study the regulation of autoreactive B cells in normal mice and the loss of regulation in autoimmune-prone animals, we have used transgenic (Tg) mouse models to ask how B cells which express a disease-related autoantibody, Rheumatoid Factor (RF), are prevented from causing harm in normal mice. We first demonstrated that these cells develop, mature and are immunocompetent in non-autoimmune mice (Hannum et al., 1996). Recent results demonstrate that these Tg RF B cells are spontaneously activated in autoimmune-prone mice, but only when the autoantigen is present (Wang and Shlomchik, 1999). We have recently used this system to develop a method to visualize the initiating events of B cell autoimmunity (William et al., 2005a; William et al., 2005b), an elusive goal. We expect this to be a powerful new model system for understanding of the origins of autoimmunity. For example, we have recently found that the early and perhaps chronic events in the MRL.Faslpr lupus model are not taking place in the germinal center (GC) as originally thought, but instead involve continuous proliferation at the outer edge of the T cell zone, where T and B cells normally interact only transiently (William et al., 2002). Quite surprisingly, we have shown that very active somatic hypermutation of Ig V regions is taking place at this site, thus dissociating mutation from the GC environment for the first time and also raising the possibility that mutation outside of GCs can lead to loss of self-tolerance (William et al., 2002). Interestingly, we found that autoreactive B cells on a normal BALB/c background still entered GCs and began to mutate there, but never made autoantibodies, thus suggesting a new self-tolerance checkpoint. We are actively investigating how autoreactive B cells become activated at extrafollicular sites, using a new method that we discovered to induce it (rather than wait for it to happen spontaneously) as well as a cell transfer system. These techniques greatly improve our ability to dissect the mechanisms. We are currently investigating the roles of TLRs, DCs, T cells, BAFF/APRIL family members and other costimulatory molecules using a combination of knockout mice and inhibitors. We also recently developed a BCR knockin version of the AM14 mouse, which undergoes isotype switch. This facilitates our identification of activated cells, the study of switch regulation, and also the development of memory.
An emerging interest in this area is the role of Toll-like receptors in activating autoreactive B cells (Leadbetter et al., 2002, Vigliante et al., 2003, Christensen, et al., submitted, 2005). These studies, partly in collaboration with Dr. Marshak-Rothstein at Boston University, have provided significant new insights into how self-Ags stimulate the immune system in autoimmunity by stimulating TLRs. In two recent studies, we have shown how this explains the generation of the two major types of lupus-related autoantibodies, anti-DNA and anti-RNA. Using knockout mice, we showed that the former is controlled by TLR9 and the latter by TLR7. Surprisingly though, we found that while deletion of TLR7 ameliorated disease, deletion of TLR9 exacerbated it; thus, only TLR7 appears to be a good therapeutic target (Christensen et al., 2005; Christensen et al., 2006). We are currently investigating the mechanism by which TLR9 normally regulates disease, as well as the cell types that need to express both TLRs to promote disease.
An important related focus has been on how activated autoreactive B cells contribute to pathogenesis in systemic autoimmunity. Traditionally B cells have been thought of mainly as sources of pathogenic autoantibody. We challenged this view with the notion that a main function of B cells is to activate autoreactive, pathogenic T cells, in an antigen-specific way. First, we deleted B cells from autoreactive mice and showed that T cell activation and disease was ablated (Chan and Shlomchik, 1998; Shlomchik et al., 1994). Second, we created a novel mouse model which had B cells expressing only the membrane form of IgM and that could not secrete Ab (Chan et al., 1999). In the autoimmune-prone mouse, such B cells promoted both T cell activation and disease. We have recently developed a Tg mouse that expresses human CD20 on all B cells and can be used to deplete B cells with anti-CD20 at any time. Using this model, we recently found that depletion of B cells in adult autoimmune-prone mice can indeed ameliorate disease, but at the same time we discovered that depleting B cells in the midst of autoimmunity is markedly more difficult than in normal strains, thus revealing an unexpected therapeutic barrier (Ahuja, et al, submitted). We are now working on why this is the case.
The second major interest in B cell biology is the development of high affinity B cell immune responses and memory. We are using a Tg mouse model which has B cells that cannot secrete antibody to explore whether antigen retained as immune complexes on follicular dendritic cells (FDCs) is necessary for the development and maintenance of memory B cells. B cells in these mice make normal primary and secondary immune responses including germinal centers and somatic mutation (Hannum et al., 2000). We have also recently found that normal memory B cells form in these animals survive without further cell division for months after their initial development (Anderson et al., 2006b). Thus, immune complexes on FDCs are not necessary for these processes. We are now investigating the identity and functional capacity of the memory cells formed and have used microarray expression profiling to identify a host of genes differentially expressed between naïve and memory B cells. Many of these have been confirmed at the protein level, providing new insights into the functions of memory B cells. We are currently using knockout mice to test the roles of some of these molecules in memory development and function in vivo We also have a program to study the dynamics of germinal center B cells using both experimental and computer modeling approaches, as well as in vivo multiphoton microscopy, a program led by Associate Research Scientist Dr. Ann Haberman (Hauser, et al., submitted).
Over the past several years we have developed an interest in the immunopathology surrounding stem cell transplantation We have focused on chronic GVHD (cGVHD), applying modern genetics and molecular techniques to a murine model. We have already shown (surprisingly) that host-derived antigen-presenting cells are not required to induce cGVHD. Further, we have found that host-derived CD4+/CD25+ T cells play an important role in regulating cGVHD (Anderson et al., 2005; Anderson et al., 2004). Most recently, in collaboration with Dr. Warren Shlomchik, we found that donor memory T cells do not cause GVHD, although they engraft and function (Anderson et al., 2003). This could represent a major therapeutic approach to minimize GVHD while preserving GVL and immunocompetence in recipients. We are currently investigating the reasons why memory T cells do not cause GVHD.
If you are interested in working on or discussing any of these areas, feel free to contact me anytime.
Other Expertise
Academic Experience:
I wish to be contacted by interested students (medical, graduate or undergraduates) as a potential research mentor/thesis advisor.
Section Editor, Journal of Immunology
Study Section, Arthritis Foundation
I wish to be contacted by interested students (medical, graduate or undergraduates) as a potential research mentor/thesis advisor.
Section Editor, Journal of Immunology
Study Section, Arthritis Foundation
Industrial Relevance
Our work on B cells in autoimmune diseases has a high degree of relevance to new therapies. We have an animal model for B cell depletion using human-specific reagents. We also have a rapid model system (one week time course) for testing the effects of potential therapeutics on autoreactive B cell activation in vivo.
Keywords
COS Keywords:
Autoimmunity, Blood Or Blood Products Or Transfusions, Bone Marrow Transplantation, Immunobiology, Immunology, Immunopathology, Immunotherapy, Lymphocytes, Molecular Cellular Entities, Stem Cells, Transgenic Animals.Additional Terms:
Autoimmunity, B Cell Development, B Cell Memory, Graft vs. Host Disease, Immunologic Tolerance, Transgenic Mouse.Languages
(Reading, Writing, Speaking)
Spanish: (Fluent, Functional, Functional)
Memberships
Alpha Omega Alpha
American Association for the Advancement of Science
American Association of Blood Banks
American Association of Immunologists
American Society for Clinical Investigation
American Society for Hematology
New York Academy of Sciences
Honors and Awards
2006, Einbender Distinguished Lecture,
University of Missouri School of Medicine
2004, Elected Member,
American Society for Clinical Investigation
Previous Positions
1991-1993, Postdoctoral Fellow,
Fox Chase Cancer Center
Funding Received
- National Institutes of Health (NIH): Disregulation of the Immune System in Autoimmunity: PI: Subproject 3: Regulation of Rheumatoid Factor bearing B cells in normal and autoimmune-prone mice, $245,083, Sep 30, 2002 to Mar 31, 2007.
- National Institutes of Health (NIH): Is Antigen Retained on FDC Required for B cell Memory?, $129,000, Sep 1, 1998 to Aug 31, 2003.
- National Institutes of Health (NIH): Mechanisms of Chronic GVHD Initiation and Pathogenesis, $225,000, Jan 1, 2001 to Dec 31, 2004.
- National Institutes of Health (NIH): The Roles of B cells and DCs in lupus T cell pathogenesis, $213,750, Aug 1, 2001 to Jul 31, 2006.
Publications
- O'Neill SK, Shlomchik MJ, Glant TT, Cao Y, Doodes PD, Finnegan A, Antigen-specific B Cells Are Required As APCs and Autoantibody-producing
Cells for Induction of Severe Autoimmune Arthritis., Journal of Immunology (baltimore, Md. : 1950), 174(6), 3781-8, Mar 2005
- Anderson BE, McNiff JM, Jain D, Blazar BR, Shlomchik WD, Shlomchik MJ, Distinct Roles for Donor- and Host-derived Antigen-presenting Cells And
Costimulatory Molecules in Murine Chronic Graft-versus-host Disease:
Requirements Depend on Target Organ., Blood, 105(5), 2227-34, Mar 2005
- Bach JF, Bendelac A, Brenner MB, Cantor H, De Libero G, Kronenberg M, Lanier LL, Raulet DH, Shlomchik MJ, von Herrath MG, The Role of Innate Immunity in Autoimmunity., The Journal of Experimental Medicine, 200(12), 1527-31, Dec 2004
- Shlomchik MJ, Cooke A, Weigert M, Autoimmunity: the Genes and Phenotypes of Autoimmunity., Current Opinion in Immunology, 16(6), 738-40, Dec 2004
- Kaplan DH, Anderson BE, McNiff JM, Jain D, Shlomchik MJ, Shlomchik WD, Target Antigens Determine Graft-versus-host Disease Phenotype., Journal of Immunology (baltimore, Md. : 1950), 173(9), 5467-75, Nov 2004
- Wong FS, Wen L, Tang M, Ramanathan M, Visintin I, Daugherty J, Hannum LG, Janeway CA Jr, Shlomchik MJ, Investigation of the Role of B-cells in Type 1 Diabetes in the NOD Mouse., Diabetes, 53(10), 2581-7, Oct 2004
- Anderson BE, McNiff JM, Matte C, Athanasiadis I, Shlomchik WD, Shlomchik MJ, Recipient CD4+ T Cells That Survive Irradiation Regulate Chronic
Graft-versus-host Disease., Blood, 104(5), 1565-73, Sep 2004
- Viglianti GA, Lau CM, Hanley TM, Miko BA, Shlomchik MJ, Marshak-Rothstein A, Activation of autoreactive B cells by CpG dsDNA, Immunity, 19(6), 837-47, 2003
- Kleinstein SH, Louzoun Y, Shlomchik MJ, Estimating hypermutation rates from clonal tree data, Journal of Immunology (baltimore, Md. : 1950), 171(9), 4639-49, 2003
- Rossbacher J and Shlomchik MJ, The B Cell Receptor Itself Can Activate Complement to Provide the Complement Receptor 1/2 Ligand Required to Enhance B Cell Immune Responses In Vivo, Journal of Experimental Medicine, 198(4), 591-602, 18 Aug 2003
- Anderson BE, McNiff J, Yan J, Doyle H, Mamula M, Shlomchik MJ, Shlomchik WD, Memory CD4+ T cells do not induce graft-versus-host disease, Journal of Clinical Investigation, 112(1), 101-8, July 2003
- Shlomchik MJ, Madaio MP, The role of antibodies and B cells in the pathogenesis of lupus nephritis, Springer Seminars in Immunopathology, 24(4), 363-75, 2003
- Shlomchik MJ, Euler CW, Christensen SC, William J, Activation of rheumatoid factor (RF) B cells and somatic hypermutation
outside of germinal centers in autoimmune-prone MRL/lpr
mice, Annals of the New York Academy of Sciences, 987, 38-50, April 2003
- Haberman AM, William J, Euler C, Shlomchik MJ, Rheumatoid factors in health and disease: structure, function, induction
and regulation, Current Directions in Autoimmunity, 6, 169-95, 2003
- William J, Euler C, Christensen S, Shlomchik MJ, Evolution of autoantibody responses via somatic hypermutation outside of
germinal centers, Science, 297(5589), 2066-70, September 2002
- Leadbetter EA, Rifkin IR, Hohlbaum AM, Beaudette BC, Shlomchik MJ, Marshak-Rothstein A, Chromatin-IgG complexes activate B cells by dual engagement of IgM and
Toll-like receptors, Nature, 416(6881), 603-7, April 2002
- Ramakrishna C, Stohlman SA, Atkinson RD, Shlomchik MJ, Bergmann CC, Mechanisms of central nervous system viral persistence: the critical role
of antibody and B cells, Journal of Immunology (baltimore, Md. : 1950), 168(3), 1204-11, February 2002
- Liu J, Anderson BE, Robert ME, McNiff JM, Emerson SG, Shlomchik WD, Shlomchik MJ, Selective T-cell subset ablation demonstrates a role for T1 and T2 cells
in ongoing acute graft-versus-host disease: a model system for the
reversal of disease, Blood, 98(12), 3367-75, December 2001
- Matthews AE, Weiss SR, Shlomchik MJ, Hannum LG, Gombold JL, Paterson Y, Antibody is required for clearance of infectious murine hepatitis virus
A59 from the central nervous system, but not the liver, Journal of Immunology (baltimore, Md. : 1950), 167(9), 5254-63, November 2001
- Shlomchik MJ, Craft JE, Mamula MJ, From T to B and back again: positive feedback in systemic autoimmune
disease, Nature Reviews. Immunology, 1(2), 147-53, November 2001
- Chan OT, Paliwal V, McNiff JM, Park SH, Bendelac A, Shlomchik MJ, Deficiency in beta(2)-microglobulin, but not CD1, accelerates spontaneous
lupus skin disease while inhibiting nephritis in MRL-Fas(lpr) nice: an
example of disease regulation at the organ, Journal of Immunology (baltimore, Md. : 1950), 167(5), 2985-90, September 2001
- Shlomchik MJ, Radebold K, Duclos N, Manuelidis L, Neuroinvasion by a Creutzfeldt-Jakob disease agent in the absence of B cells and follicular dendritic cells, Proceedings of the National Academy of Sciences (USA), 98(16), 9289-94, 2001
- Debelak J, Shlomchik MJ, Snyder EL, Cooper D, Seropian S, McGuirk J, Smith B, Krause DS, Isolation and flow cytometric analysis of T-cell-depleted CD34+ PBPCs, Transfusion, 40(12), 1475-81, December 2000
- Hannum LG, Haberman AM, Anderson SM, Shlomchik MJ, Germinal center initiation, variable gene region hypermutation, and mutant B cell selection without detectable immune complexes on follicular dendritic cells, Journal of Experimental Medicine, 192(7), 931-42, 2000
- Rifkin IR, Leadbetter EA, Beaudette BC, Kiani C, Monestier M, Shlomchik MJ, Marshak-Rothstein A, Immune complexes present in the sera of autoimmune mice activate rheumatoid factor B cells, Journal of Immunology, 165(3), 1626-33, 2000
- Kima PE, Constant SL, Hannum L, Colmenares M, Lee KS, Haberman AM, Shlomchik MJ, McMahon-Pratt D, Internalization of Leishmania mexicana complex amastigotes via the Fc receptor is required to sustain infection in murine cutaneous leishmaniasis., Journal of Experimental Medicine, 191(6), 1063-8, 20 2000
- Levine MH, Haberman AM, Sant'Angelo DB, Hannum LG, Cancro MP, Janeway CA, Shlomchik MJ, A B-cell receptor-specific selection step governs immature to mature B cell differentiation, Proceedings of the National Academy of Sciences (USA), 97(6), 2743-8, 2000
- Chan OT, Shlomchik MJ, Cutting edge: B cells promote CD8+ T cell activation in MRL-Fas\(lpr\) mice independently of MHC class I antigen presentation., Journal of Immunology, 164(4), 1658-62, 15 2000
- Macy JD, Weir EC, Compton SR, Shlomchik MJ, Brownstein DG, Dual infection with Pneumocystis carinii and Pasteurella pneumotropica in B cell-deficient mice: diagnosis and therapy, Comparative Medicine, 50(1), 49-55, February 2000
- Golovkina TV, Shlomchik M, Hannum L, Chervonsky A, Organogenic role of B lymphocytes in mucosal immunity, Science, 286(5446), 1965-8, December 1999
- Chan OT, Madaio MP, Shlomchik MJ, B cells are required for lupus nephritis in the polygenic, Fas-intact MRL model of systemic autoimmunity, Journal of Immunology, 163(7), 3592-6, October 1999
- Wang H, Shlomchik MJ, Autoantigen-specific B cell activation in Fas-deficient rheumatoid factor immunoglobulin transgenic mice, Journal of Experimental Medicine, 190(5), 639-49, September 1999
- Shlomchik WD, Couzens MS, Tang CB, McNiff J, Robert ME, Liu J, Shlomchik MJ, Emerson SG, Prevention of graft versus host disease by inactivation of host antigen-presenting cells, Science, 285(5426), 412-5, July 1999
- Chan OT, Madaio MP, Shlomchik MJ, The central and multiple roles of B cells in lupus pathogenesis, Immunological Reviews, 169, 107-21, June 1999
- Chan OT, Hannum LG, Haberman AM, Madaio MP, Shlomchik MJ, A novel mouse with B cells but lacking serum antibody reveals an antibody-independent role for B cells in murine lupus, Journal of Experimental Medicine, 189(10), 1639-48, May 1999
- Dal Porto JM, Haberman AM, Shlomchik MJ, Kelsoe G, Antigen drives very low affinity B cells to become plasmacytes and enter germinal centers, Journal of Immunology, 161(10), 5373-81, November 1998
- Wang H, Shlomchik MJ, Maternal Ig mediates neonatal tolerance in rheumatoid factor transgenic mice but tolerance breaks down in adult mice, Journal of Immunology, 160(5), 2263-71, March 1998
- Wang H, Shlomchik MJ, Maternal Ig mediates neonatal tolerance in rheumatoid factor transgenic mice but tolerance breaks down in adult mice., Journal of Immunology, 160(5), 2263-71, 1 1998
- Shlomchik M J, Watts P, Weigert M G, Litwin S, Clone: a Monte-Carlo computer simulation of B cell clonal expansion, somatic mutation, and antigen-driven selection., Current Topics In Microbiology and Immunology, 229, 173-97, 1998
- Chan O, Shlomchik MJ, A new role for B cells in systemic autoimmunity: B cells promote spontaneous T cell activation in MRL-lpr/lpr mice, Journal of Immunology, 160(1), 51-9, Jan 1998
- Chan O, Shlomchik MJ, A new role for B cells in systemic autoimmunity: B cells promote spontaneous T cell activation in MRL-lpr/lpr mice., Journal of Immunology, 160(1), 51-9, 1 1998
- Stewart JJ, Lee CY, Ibrahim S, Watts P, Shlomchik M, Weigert M, Litwin S, A Shannon entropy analysis of immunoglobulin and T cell receptor, Molecular Immunology, 34(15), 1067-82, October 1997
- Wang H, Shlomchik MJ, High affinity rheumatoid factor transgenic B cells are eliminated in normal mice, Journal of Immunology, 159(3), 1125-34, August 1997
- Stewart JJ, Agosto H, Litwin S, Welsh JD, Shlomchik M, Weigert M, Seiden PE, A solution to the rheumatoid factor paradox: pathologic rheumatoid factors can be tolerized by competition with natural rheumatoid factors, Journal of Immunology, 159(4), 1728-38, August 1997
- Chan O, Madaio M P, Shlomchik M J, The roles of B cells in MRL/lpr murine lupus., Annals of The New York Academy of Sciences, 815, 75-87, 5 Apr 1997
- Madaio M P, Shlomchik M J, Emerging concepts regarding B cells and autoantibodies in murine lupus nephritis. B cells have multiple roles; all autoantibodies are not equal, Journal of The American Society of Nephrology, 7(3), 387-96, March 1996
- Shan H, Shlomchik MJ, Marshak-Rothstein A, Pisetsky DS, Litwin S, Weigert MG, The mechanism of autoantibody production in an autoimmune MRL/lpr mouse, Journal of Immunology, 153(11), 5104-20, December 1994
- Shlomchik MJ, Madaio MP, Ni D, Trounstein M, Huszar D, The role of B cells in lpr/lpr-induced autoimmunity, Journal of Experimental Medicine, 180(4), 1295-306, October 1994
- Jacobson BA, Sharon J, Shan H, Shlomchik M, Weigert MG, Marshak-Rothstein A, An isotype switched and somatically mutated rheumatoid factor clone isolated from a MRL-lpr/lpr mouse exhibits limited intraclonal affinity maturation, Journal of Immunology, 152(9), 4489-99, May 1994
- Shlomchik MJ, Zharhary D, Saunders T, Camper SA, Weigert MG, A rheumatoid factor transgenic mouse model of autoantibody regulation, International Immunology, 5(10), 1329-41, October 1993
- Bloom DD, Davignon JL, Retter MW, Shlomchik MJ, Pisetsky DS, Cohen PL, Eisenberg RA, Clarke SH, V region gene analysis of anti-Sm hybridomas from MRL/Mp-lpr/lpr mice, Journal of Immunology, 150(4), 1591-610, February 1993
- Tutter A, Brodeur P, Shlomchik M, Riblet R, Structure, map position, and evolution of two newly diverged mouse Ig VH gene families, Journal of Immunology, 147(9), 3215-23, November 1991
- Matzuk MM, Shlomchik M, Shaw LM, Making digoxin therapeutic drug monitoring more effective, Therapeutic Drug Monitoring, 13(3), 215-9, May 1991
- Shlomchik M, Weigert M, Is the hypothesis alive that IgM anti-IgG1 rheumatoid factor specificity is determined by framework regions?, European Journal of Immunology, 20(11), 2529-31, November 1990
- Shan H, Shlomchik M, Weigert M, Heavy-chain class switch does not terminate somatic mutation, Journal of Experimental Medicine, 172(2), 531-6, August 1990
- Litwin S, Shlomchik M, A test for clonal relatedness in a set of lymphocytes., Journal of Experimental Medicine, 171(1), 293-7, 1 Jan 1990
- Shlomchik M, Mascelli M, Shan H, Radic MZ, Pisetsky D, Marshak-Rothstein A, Weigert M, Anti-DNA antibodies from autoimmune mice arise by clonal expansion and somatic mutation, Journal of Experimental Medicine, 171(1), 265-92, January 1990
- Radic M Z, Mascelli M A, Erikson J, Shan H, Shlomchik M, Weigert M, Structural patterns in anti-DNA antibodies from MRL/lpr mice., Cold Spring Harbor Symposia On Quantitative Biology, 54 Pt 2, 933-46, 1989
- Shlomchik MJ, Aucoin AH, Pisetsky DS, Weigert MG, Structure and function of anti-DNA autoantibodies derived from a single autoimmune mouse, Proceedings of the National Academy of Sciences (USA), 84(24), 9150-4, December 1987
- Shlomchik MJ, Marshak-Rothstein A, Wolfowicz CB, Rothstein TL, Weigert MG, The role of clonal selection and somatic mutation in autoimmunity, Nature, 328(6133), 805-11, August 1987
- Shlomchik M, Nemazee D, van Snick J, Weigert M, Variable region sequences of murine IgM anti-IgG monoclonal autoantibodies (rheumatoid factors). II. Comparison of hybridomas derived by lipopolysaccharide stimulation and secondary protein immunizati, Journal of Experimental Medicine, 165(4), 970-87, April 1987
- Shlomchik MJ, Nemazee DA, Sato VL, Van Snick J, Carson DA, Weigert MG, Variable region sequences of murine IgM anti-IgG monoclonal autoantibodies (rheumatoid factors). A structural explanation for the high frequency of IgM anti-IgG B cells, Journal of Experimental Medicine, 164(2), 407-27, August 1986
Profile Details
Last Updated: 6/3/2007
COS Expertise ID #397133
Reference this profile directly: http://myprofile.cos.com/mshlomchik
Individual Expertise profile of Mark Jay Shlomchik, Copyright Mark Jay Shlomchik.
© COS ExpertiseTM, 2009, ProQuest LLC All rights reserved.