Immunoglobulin synthesis and generalized autoimmunity in mice congenitally deficient in alpha beta(+) T cells.
Through cognate B-cell-T-cell interactions and provision of cytokines, CD4+ T-cell antigen receptor (TCR) alpha beta+ T cells regulate immunoglobulin isotype synthesis. Murine IgG1 and IgE secretion is therefore substantially T-cell-dependent, whereas IgM and IgG3 secretion is not. Here we report that in the absence of alpha beta T cells, B cells expand, differentiate and secrete copious amounts of antibodies of 'T-dependent' isotypes. Moreover, the antibodies are reactive towards self-antigens, as in patients with systemic lupus erythematosus, so autoantibodies of 'T-dependent' type can develop without the help of CD4+ alpha beta T cells. This phenotype is not evident in mice or humans that are congenitally deficient in specific alpha beta T-cell functions, but bears comparison with B-cell hyperactivity and autoimmunity in transplant rejection and in immunodeficiencies such as AIDS.
Wen
L
L
Department of Biology, Yale University, New Haven, Connecticut 06511.
Roberts
S J
SJ
Viney
J L
JL
Wong
F S
FS
Mallick
C
C
Findly
R C
RC
Peng
Q
Q
Craft
J E
JE
Owen
M J
MJ
Hayday
A C
AC
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis*; D007153:Immunologic Deficiency Syndromes / Q000151:congenital / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*
D001323:Autoantibodies; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D016693:Receptors, Antigen, T-Cell, alpha-beta; D007073:Immunoglobulin E