Contribution of alphabeta and gammadelta T cells to the generation of primary immunoglobulin G-driven autoimmune response in immunoglobulin- mu-deficient/lpr mice.
Class switch recombination (CSR) is a T-cell-dependent mechanism regulating isotype switching in activated mature B cells. Recently we showed that T-cell-independent CSRs occur spontaneously during B lymphopoiesis, but such cells are negatively selected by Fas signalling. In immunoglobulin mu-deficient mice, lack of Fas rescues isotype-switched B cells, resulting in generation of an autoimmune primary immunoglobulin G (IgG) repertoire in muMT/lpr mice. In the present study, we studied the role of alphabeta and gammadelta T cells in regulating this primary gammaH-driven repertoire. We found that a lack of alphabeta T cells significantly inhibited IgG production and autoimmunity in muMT/lpr mice, whereas a lack of gammadelta T cells resulted in augmented IgG production and autoimmunity. Also, a lack of T cells in muMT mice rescued isotype-switched B cells and serum IgG, probably owing to the lack of available FasL. We suggest that although CSRs in B-cell lymphopoiesis are T-cell independent, alphabeta T cells are important in the expansion of isotype-switched B-cell precursors and in promoting gammaH-driven autoimmunity, whereas gammadelta T cells regulate these cells.
Seagal
Jane
J
Department of Immunology, Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Melamed
Doron
D
D000818:Animals; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002843:Chromatin / Q000276:immunology; D053222:Fas Ligand Protein; D017578:Immunoglobulin Class Switching / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000097:blood; D007148:Immunoglobulin mu-Chains / Q000276:immunology; D008211:Lymphocyte Cooperation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D019014:fas Receptor / Q000276:immunology
D002843:Chromatin; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007074:Immunoglobulin G; D007148:Immunoglobulin mu-Chains; D008562:Membrane Glycoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D019014:fas Receptor