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

J Immunol. 2002 Mar 15;168(6):2676-82. doi: 10.4049/jimmunol.168.6.2676.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Antibodies, Anti-Idiotypic / pharmacology
  • Antibodies, Monoclonal / pharmacology
  • Antigens, Differentiation, B-Lymphocyte / biosynthesis
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • CD40 Ligand / pharmacology*
  • CD40 Ligand / physiology
  • Cell Differentiation / immunology
  • Cell Division / immunology
  • Cells, Cultured
  • Cross-Linking Reagents / metabolism*
  • Down-Regulation / immunology*
  • Female
  • Immunoglobulin Class Switching / immunology*
  • Immunoglobulin D / immunology
  • Immunoglobulin E / biosynthesis
  • Immunoglobulin G / biosynthesis
  • Interleukin-4 / pharmacology*
  • Male
  • Mice
  • Mice, Inbred CBA
  • Receptors, Antigen, B-Cell / metabolism*
  • Recombinant Proteins / pharmacology

Substances

  • Adjuvants, Immunologic
  • Antibodies, Anti-Idiotypic
  • Antibodies, Monoclonal
  • Antigens, Differentiation, B-Lymphocyte
  • Cross-Linking Reagents
  • Immunoglobulin D
  • Immunoglobulin G
  • Receptors, Antigen, B-Cell
  • Recombinant Proteins
  • anti-IgD
  • CD40 Ligand
  • Interleukin-4
  • Immunoglobulin E