title: Cross-linking surface Ig delays CD40 ligand- and IL-4-induced B cell Ig class switching and reveals evidence for independent regulation of B cell proliferation and differentiation.
abstract: T cells stimulate B cells to divide and differentiate by providing activating signals in the form of inducible membrane-bound molecules and secreted cytokines. Provision of these signals in vitro reproduces many of the consequences of T-B collaboration in the absence of any form of Ag stimulation. Although clearly not obligatory, Ag signals appear to play an important regulatory role in numerous aspects of the B cell response. To examine directly the effect of an Ag signal, naive B cells were stimulated in the presence of rCD40 ligand, with or without IL-4 in the presence or absence of different anti-Ig mAbs. Anti-Ig mAbs exerted variable effects on the B cell division rate, from enhancement to no effect to inhibition. In contrast, all anti-Ig mAbs tested inhibited division-linked isotype switching to IgG1 and IgE. Thus, B cell Ag receptor ligands could modify the rates of B cell expansion and class switching independently. The ability of anti-Ig reagents to modify class switching suggests the B cell Ag receptor may play an important role in the selection of Ig isotypes during T cell-dependent humoral immune responses to Ags of different physical structure.
authors.affiliation: Immune Regulation Group, Medical Foundation of the University of Sydney, Centenary Institute of Cell Biology and Cancer Research, Sydney, Australia. james.rush@yale.edu
authors.forename: James S
authors.initials: JS
authors.lastname: Rush
authors.forename: Jhagvaral
authors.initials: J
authors.lastname: Hasbold
authors.forename: Philip D
authors.initials: PD
authors.lastname: Hodgkin
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D023201:CD40 Ligand / Q000494:pharmacology* / Q000502:physiology; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D003432:Cross-Linking Reagents / Q000378:metabolism*; D015536:Down-Regulation / Q000276:immunology*; D005260:Female; D017578:Immunoglobulin Class Switching / Q000276:immunology*; D007072:Immunoglobulin D / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D015847:Interleukin-4 / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D000276:Adjuvants, Immunologic; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000944:Antigens, Differentiation, B-Lymphocyte; D003432:Cross-Linking Reagents; D007072:Immunoglobulin D; D007074:Immunoglobulin G; D011947:Receptors, Antigen, B-Cell; D011994:Recombinant Proteins; C039951:anti-IgD; D023201:CD40 Ligand; D015847:Interleukin-4; D007073:Immunoglobulin E