CD28 is required for germinal center formation

J Immunol. 1996 Jun 15;156(12):4576-81.

Abstract

Previous studies have demonstrated that the T cell costimulatory molecule, CD28, is important in the development of humoral immunity. CD28-deficient mice exhibit defects in isotype switching and are more susceptible to pathogens that depend on an effective Ab response. To determine the basis of these defects, we have examined B cell responses of CD28-deficient mice at the microenvironmental level. Early in a normal T-dependent immune response, small numbers of B cells undergo activation in the T cell-rich zone of secondary lymphoid tissues and then migrate to B cell areas. These migrant B cells found developing germinal centers by proliferative expansion, during which individual cells acquire mutations in their rearranged Ig genes. B cell mutants retaining higher affinities for Ag undergo positive selection in germinal centers, resulting in the establishment of the memory B cell compartment. In the present study, we demonstrate that although potentially Ag-reactive cells within the lymphoid follicle accumulate following antigenic challenge, these cells fail to undergo proliferative expansion to form germinal centers and do not acquire somatic mutations in CD28-deficient animals. Thus, the CD28 activation pathway is required for Ab responses to T-dependent Ags. cell compartment. In the present study, we demonstrate that although potentially Ag-reactive cells within the lymphoid follicle accumulate following antigenic challenge, these cells fail to undergo proliferative expansion to form germinal centers and do not acquire somatic mutations in CD28-deficient animals. Thus, the CD28 activation pathway is required for Ab responses to T-dependent Ags.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibody Formation
  • CD28 Antigens / physiology*
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain
  • Genes, Immunoglobulin
  • Germinal Center / cytology*
  • Immunoglobulin A / metabolism
  • Immunoglobulin Variable Region / genetics
  • Mice
  • Mice, Knockout
  • Peyer's Patches / cytology*
  • Spleen / cytology*

Substances

  • CD28 Antigens
  • Immunoglobulin A
  • Immunoglobulin Variable Region