SH2D1A regulates T-dependent humoral autoimmunity.
The signaling lymphocytic activation molecule (SLAM)/CD150 family includes a family of chromosome 1-encoded cell surface molecules with costimulatory functions mediated in part by the adaptor protein SH2D1A (SLAM-associated protein, SAP). Deficiency in SH2D1A protects mice from an experimental model of lupus, including the development of hypergammaglobulinemia, autoantibodies including anti-double stranded DNA, and renal disease. This protection did not reflect grossly defective T or B cell function per se because SH2D1A-deficient mice were susceptible to experimental autoimmune encephalomyelitis, a T cell-dependent disease, and they were capable of mounting normal T-independent antigen-specific immunoglobulin responses. Instead, T-dependent antibody responses were impaired in SH2D1A-deficient mice, reflecting defective germinal center formation. These findings demonstrate a specific role for the SLAM-SH2D1A system in the regulation of T-dependent humoral immune responses, implicating members of the CD150-SH2D1A family as targets in the pathogenesis and therapy of antibody-mediated autoimmune and allergic diseases.
Hron
Jonathan D
JD
Washington University School of Medicine, Campus Box 8045, CSRB 6617, 660 S. Euclid Ave., St. Louis, MO 63110, USA.
Caplan
Liron
L
Gerth
Andrea J
AJ
Schwartzberg
Pamela L
PL
Peng
Stanford L
SL
D000818:Animals; D000917:Antibody Formation; D015703:Antigens, CD; D001327:Autoimmune Diseases / Q000276:immunology; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006023:Glycoproteins / Q000096:biosynthesis; D007136:Immunoglobulins / Q000096:biosynthesis; D047908:Intracellular Signaling Peptides and Proteins; D008177:Lupus Vulgaris / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011956:Receptors, Cell Surface; D015398:Signal Transduction; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
D015703:Antigens, CD; D002352:Carrier Proteins; D006023:Glycoproteins; D007136:Immunoglobulins; D047908:Intracellular Signaling Peptides and Proteins; D011956:Receptors, Cell Surface; C499569:Sh2d1a protein, mouse; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1