B cell function in mice transgenic for mCTLA4-H gamma 1: lack of germinal centers correlated with poor affinity maturation and class switching despite normal priming of CD4+ T cells

J Exp Med. 1994 Mar 1;179(3):819-30. doi: 10.1084/jem.179.3.819.

Abstract

This report outlines the B cell phenotype of transgenic mice that overexpresses the mouse CTLA-4-human gamma 1 (mCTLA4-H gamma 1) protein. Despite the fact that these mice prime CD4+ T cells (Ronchese, F., B. Housemann, S. Hubele, and P. Lane. 1994. J. Exp. Med. 179:809), antibody responses to T-dependent antigens are severely impaired. In contrast, T-independent responses are normal which suggests mCTLA4-H gamma 1 does not act directly on B cells, but acts indirectly by impairing T cell help. The impaired antibody defect is associated with impaired class switching, with low total immunoglobulin (Ig)G and antigen-specific IgG responses, and an absence of germinal center formation in spleen and lymph nodes but not gut-associated tissues. The defective germinal center formation is associated with a reduction in the degree of somatic mutation in hybridomas made from transgenic mice in comparison with those made from normal mice. It seems likely that mCTLA4-H gamma 1 exerts its effect by blocking an interaction between T and B cells that induce T cell help for B cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abatacept
  • Animals
  • Antibody Formation
  • Antigens, CD
  • Antigens, Differentiation / biosynthesis
  • Antigens, Differentiation / genetics*
  • Antigens, Differentiation / immunology
  • B-Lymphocytes / immunology*
  • Base Sequence
  • CD4 Antigens / immunology*
  • CTLA-4 Antigen
  • Chickens
  • DNA Primers
  • Humans
  • Immunoconjugates*
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin G / classification
  • Immunoglobulin G / genetics*
  • Immunoglobulin G / immunology
  • Immunoglobulin Heavy Chains / biosynthesis
  • Immunoglobulin Heavy Chains / genetics*
  • Lymph Nodes / immunology
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Peyer's Patches / immunology
  • Polymerase Chain Reaction
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / immunology
  • Spleen / immunology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes / immunology*
  • gamma-Globulins / immunology

Substances

  • Antigens, CD
  • Antigens, Differentiation
  • CD4 Antigens
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Ctla4 protein, mouse
  • DNA Primers
  • Immunoconjugates
  • Immunoglobulin G
  • Immunoglobulin Heavy Chains
  • Recombinant Fusion Proteins
  • gamma-Globulins
  • Abatacept

Associated data

  • GENBANK/J00534
  • GENBANK/M15228
  • GENBANK/M64142
  • GENBANK/X00160
  • GENBANK/X02066