Diminished FDC activation within germinal centers of CD19-deficient mice (92.8)

Abstract

Germinal centers (GC) are sites within secondary lymphoid organs where affinity maturation and somatic hypermutation occur, producing high affinity antibody forming cells and memory B cells. We reported previously that mice with mutant CD19 form GC with dark and light zones, although GC B cell differentiation and proliferation are defective in the light zone of these mice. We now show that PNA+ B cells are induced after SRBC immunization and form a dark zone but fail to enter the FDC (light) zone in mice that lack CD19. These mice also lack marginal zone (MZ) B cells, which have been reported to contribute to GC responses through delivery of immune complexes to follicular dendritic cells (FDC), suggesting a possible link between the lack of MZ B cells and the impaired GC reaction. Therefore, we compared GC in the spleen with those in the LN, which does not have a MZ. We used induction of VCAM-1 expression as a marker for FDC activation. Immunization of CD19-deficient mice induced expression of VCAM-1 on LN FDC. In contrast, induction of VCAM-1 expression on FDC in splenic GC was severely reduced in the same mice. These data suggest distinct mechanisms for FDC activation in the LN, which is independent of CD19 on B cells, and in the spleen. In contrast to the LN, immunization fails to activate FDC in splenic GC in CD19-deficient mice, which leads to defective light zone formation. These and other data suggest that the deficiency of MZ B cells and the failure to activate FDC in mice that lack CD19 may be linked: MZ B cells may play a vital role in activation of FDC in splenic follicles that is critical for GC function. Supported by NIH R01 AI42265.