Reduced Germinal Center Formation and ITIM Signaling in B cells Relates to the Diminished Expression of FcgRII on Aged Follicular Dendritic Cells

Aging alters the structural and functional characteristics of the follicular dendritic cells (FDCs) and leads to the formation of FDCs that become atrophic, trap and retain little immune complexes (ICs). The present studies were designed to understand the age‐related function and regulation of the receptors expressed on FDCs and known to trap and retain ICs on FDCs. The level of CR1&2, Fcγ RII, FDC‐M1, and FDC‐M2 on FDCs was immunohistochemically quantitated in draining lymph nodes of actively immunized mice for 10 days after Ag challenge. Initially, FDC Fcγ RII levels were similar but by day 3 a drastic reduction in FDC‐Fcγ RII expression was apparent in old mice. FDC‐M2 labeling, reflecting IC trapping, was also reduced and correlated with a dramatic reduction in germinal center (GC) B cells as indicated by reduced GC size and number. Nevertheless, labeling of FDC‐reticula with FDC‐M1 and anti‐CR1&2 was preserved indicating that FDCs were present. FDCs in active GCs normally express high levels of FcRs that are thought to bind Fc portions of Abs in ICs and minimize their binding to FcRs on B cells. Thus, cross‐linking of BCR and FcR via IC is minimized thereby reducing signaling via the immunoreceptor tyrosine‐base inhibition motif (ITIM). Old FDCs taken at day 3, when they lack Fcγ RII, were incapable of preventing ITIM signaling in wild‐type B cells but old FDCs stimulated B cells from Fcγ RIIB −/ − mice to produce near normal levels of specific Ab. The present data support the concept that FcR are regulated abnormally on old FDCs. This abnormality correlates with a reduced IC‐retention and with a reduced capacity of FDCs to present ICs in a way that will activate GC B cells.