Impaired germinal centre formation and humoral immune response in the absence of CD28 and interleukin-4.
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.
Reiter
Rudolph
R
Institute of Medical Microbiology, Immunology and Hygiene,Technical University of Munich, Munich, Germany. rudolf.reiter@lrz.tu-muenchen.de
Pfeffer
Klaus
K
D000818:Animals; D018106:CD28 Antigens / Q000235:genetics / Q000276:immunology*; D018858:Germinal Center / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology*; D017578:Immunoglobulin Class Switching / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology
D018106:CD28 Antigens; D007074:Immunoglobulin G; D015847:Interleukin-4; D010047:Ovalbumin