Impaired germinal centre formation and humoral immune response in the absence of CD28 and interleukin-4

Immunology. 2002 Jun;106(2):222-8. doi: 10.1046/j.1365-2567.2002.01405.x.

Abstract

The generation of an optimal humoral immune response requires fully activated T-cells. For complete activation at least two signals are needed. The first one is an antigen dependent one via the T cell receptor, the second one is a costimulatory signal which can be delivered by the CD28 molecule after binding to CD80 (B7.1) or CD86 (B7.2). Fully activated T helper cells are competent to deliver help to B-cells by secreting cytokines (e.g. interleukin (IL)-4) or up-regulating CD40 ligand for proliferation and differentiation of B cells. These interactions mainly take place in germinal centres (GC) that arise after antigen stimulation in B cell-follicles of peripheral lymphatic tissues and are the sites of massive B-cell proliferation, affinity maturation and class switch. The roles of CD28 and IL-4 were investigated in GC formation and antibody production. A markedly diminished humoral immune response was observed in IL-4(-/-) xCD28(-/-) mice whereas in CD28(-/-) and IL-4(-/-) mice the defect was less severe. Especially the formation of germinal centres was significantly reduced in CD28(-/-) or IL-4(-/-) mice and almost undetectable in IL-4(-/-) xCD28(-/-) mice. Taken together these data indicate that CD28 and IL-4 are synergistically involved in GC formation and immunoglobulin production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD28 Antigens / genetics
  • CD28 Antigens / immunology*
  • Germinal Center / immunology*
  • Immune Tolerance / immunology*
  • Immunoglobulin Class Switching / immunology
  • Immunoglobulin G / biosynthesis
  • Interleukin-4 / genetics
  • Interleukin-4 / immunology*
  • Mice
  • Mice, Knockout
  • Ovalbumin / immunology

Substances

  • CD28 Antigens
  • Immunoglobulin G
  • Interleukin-4
  • Ovalbumin