CD28 is required for germinal center formation.
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.
Ferguson
S E
SE
Department of Medicine, Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, IL 60637, USA.
Han
S
S
Kelsoe
G
G
Thompson
C B
CB
D000818:Animals; D000917:Antibody Formation; D018106:CD28 Antigens / Q000502:physiology*; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D018858:Germinal Center / Q000166:cytology*; D007070:Immunoglobulin A / Q000378:metabolism; D007135:Immunoglobulin Variable Region / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D010581:Peyer's Patches / Q000166:cytology*; D013154:Spleen / Q000166:cytology*
D018106:CD28 Antigens; D007070:Immunoglobulin A; D007135:Immunoglobulin Variable Region