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

Open Access
Publisher Website
Google Scholar
Abstract
Summary: 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−/−×CD28−/− 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−/−×CD28−/− mice. Taken together these data indicate that CD28 and IL‐4 are synergistically involved in GC formation and immunoglobulin production.