A new role of CTLA-4 on B cells in thymus-dependent immune responses in vivo.
The expression of CTLA-4 (CD152) on the cell surface of B cells and its consequences for the humoral immune response in vivo are unknown. We investigated the expression of CTLA-4 mRNA and protein in B cells in T cell-independent or -dependent ways. B cells in the presence of Ag-stimulated Th2 cells expressed mRNA of CTLA-4 and up-regulated intracellular CTLA-4 protein. Using a liposome-enhanced staining technique, we show for the first time, that surface CTLA-4 protein is expressed by 11-15% of B cells in a T cell-dependent culture system. To dissect the role of CTLA-4 on B cells in vivo, we used bone marrow chimeric mice in which only B cells were CTLA-4 deficient. These mice showed that early B cell development and homeostasis is not influenced by CTLA-4 deficiency of B cells. Ag-specific responses after immunization of the chimeric mice revealed elevated levels of IgM Abs in mice deficient for B cell CTLA-4. We propose that CTLA-4 signals on B cells determine the early fate of B cells in thymus-dependent immune responses.
Quandt
Dagmar
D
Deutsches Rheuma-Forschungszentrum, Berlin, Germany.
Hoff
Holger
H
Rudolph
Marion
M
Fillatreau
Simon
S
Brunner-Weinzierl
Monika C
MC
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000502:physiology*; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology*; D060908:CTLA-4 Antigen; D002478:Cells, Cultured; D007114:Immunization; D007073:Immunoglobulin E / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D007075:Immunoglobulin M; D012333:RNA, Messenger; D007073:Immunoglobulin E