CD28 IS REQUIRED FOR GERMINAL CENTER FORMATION

Previous studies have demonstrated that the T cell costimulatory molec ule, CD28, is important in the development of humoral immunity. CD28-d eficient mice exhibit defects in isotype switching and are more suscep tible to pathogens that depend on an effective Ab response. To determi ne the basis of these defects, we have examined B cell responses of CD 28-deficient mice at the microenvironmental level. Early in a normal T -dependent immune response, small numbers of B cells undergo activatio n in the T cell-rich zone of secondary lymphoid tissues and then migra te to B cell areas. These migrant B cells found developing germinal ce nters by proliferative expansion, during which individual cells acquir e mutations in their rearranged Ig genes. B cell mutants retaining hig her affinities for Ag undergo positive selection in germinal centers, resulting in the establishment of the memory B cell compartment. In th e present study, we demonstrate that although potentially Ag-reactive cells within the lymphoid follicle accumulate following antigenic chal lenge, these cells fail to undergo proliferative expansion to form ger minal centers and do not acquire somatic mutations in CD28-deficient a nimals. Thus, the CD28 activation pathway is required for Ab responses to T-dependent Ags.