Abstract
Ag-induced B cell proliferation in vivo requires a costimulatory signal through CD40, whereas B cell Ag receptor (BCR) ligation by anti-Ig H chain Abs, such as anti-Ig micro H chain Ab and anti-Ig delta H chain Ab, alone induces proliferation of B cells in vitro, even in the absence of CD40 ligation. In this study, we demonstrate that CD40 signaling is required for survival and proliferation of B cells stimulated by protein Ags in vitro as well as in vivo. This indicates that the in vitro system represents B cell activation in vivo, and that protein Ags generate BCR signaling distinct from that by anti-Ig H chain Abs. Indeed, BCR ligation by Ags, but not by anti-Ig H chain Abs, efficiently phosphorylates the inhibitory coreceptors CD22 and CD72. When these coreceptors are activated, anti-Ig H chain Ab-stimulated B cells can survive and proliferate only in the presence of CD40 signaling. Conversely, treatment of Ag-stimulated B cells with anti-CD72 mAb blocks CD72 phosphorylation and induces proliferation, even in the absence of CD40 signaling. These results strongly suggest that activation of B cells by anti-Ig H chain Abs involves their ability to silence the inhibitory coreceptors, and that the inhibitory coreceptors install requirement of CD40 signaling for survival and proliferation of Ag-stimulated B cells.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Animals
-
Antibodies, Anti-Idiotypic* / pharmacology
-
Antigens / pharmacology*
-
Antigens, CD / metabolism
-
Antigens, CD / physiology*
-
Antigens, Differentiation, B-Lymphocyte / metabolism
-
Antigens, Differentiation, B-Lymphocyte / physiology*
-
B-Lymphocytes / cytology*
-
B-Lymphocytes / immunology*
-
B-Lymphocytes / metabolism
-
CD40 Antigens / physiology*
-
Cell Adhesion Molecules*
-
Cell Cycle / immunology
-
Cell Division / genetics
-
Cell Division / immunology
-
Cell Survival / genetics
-
Cell Survival / immunology
-
Cells, Cultured
-
Immunoglobulin Heavy Chains* / genetics
-
Immunoglobulin Heavy Chains* / immunology
-
Immunoglobulin lambda-Chains / genetics
-
Immunoglobulin lambda-Chains / immunology
-
Lectins / metabolism
-
Lectins / physiology*
-
Lymphocyte Activation / genetics
-
Mice
-
Mice, Inbred C57BL
-
Mice, Knockout
-
Nitrophenols / pharmacology
-
Phenylacetates
-
Phosphorylation
-
Receptors, Antigen, B-Cell / immunology
-
Receptors, Antigen, B-Cell / metabolism
-
Sialic Acid Binding Ig-like Lectin 2
-
Signal Transduction / genetics
-
Signal Transduction / immunology
-
Spleen / cytology
-
Spleen / immunology
-
Spleen / metabolism
Substances
-
Antibodies, Anti-Idiotypic
-
Antigens
-
Antigens, CD
-
Antigens, Differentiation, B-Lymphocyte
-
CD40 Antigens
-
CD72 protein, human
-
Cd22 protein, mouse
-
Cell Adhesion Molecules
-
Immunoglobulin Heavy Chains
-
Immunoglobulin lambda-Chains
-
Lectins
-
Nitrophenols
-
Phenylacetates
-
Receptors, Antigen, B-Cell
-
Sialic Acid Binding Ig-like Lectin 2
-
4-hydroxy-5-nitrophenyl acetic acid