FOLLICULAR DENDRITIC CELLS HELP RESTING B-CELLS TO BECOME EFFECTIVE ANTIGEN-PRESENTING CELLS - INDUCTION OF B7 BB1 AND UP-REGULATION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II MOLECULES/

This study was designed to investigate whether follicular dendritic ce lls (FDC) can activate B cells to a state in which they can function a s effective antigen-presenting cells (APC). High buoyant density (i.e. , resting) B cells specific for 2,4-dinitro-fluorobenzene (DNP) were i ncubated with DNP-ovalbumin (OVA) bearing FDC, after which their capac ity to process and present to an OVA-specific T cell clone was assesse d. The efficacies of alternative sources of antigen and activation sig nals in the induction of B cell APC function were compared with those provided by FDC. Only FDC and Sepharose beads coated with anti-immunog lobulin (Ig)kappa monoclonal antibody provided the necessary stimulus. FDC carrying inappropriate antigens also induced B cell APC function in the presence of exogenous DNP-OVA. However, in circumstances where soluble DNP-OVA was limiting, FDC bearing complexes containing DNP, wh ich could crosslink B cell Ig receptors, induced the most potent APC f unction. Analysis by flow cytometry revealed that within 24 h of cocul ture with FDC, a significant percentage of B cells increased in size a nd expressed higher levels of major histocompatibility complex class I I. By 48 h, an upregulation of the costimulatory molecule, B7/BB1, occ urred, but only when exposed to the FDC bearing DNP. Taken together, t he results demonstrate that FDC have the capacity to activate resting B cells to a state in which they can function as APC for T cells. The stimuli that FDC provide may include: (a) an antigen-dependent signal that influences the upregulation of B7/BB1; and (b) possibly a signal independent of crosslinking mIg that results in Ig internalization. Th e relevance of these findings to the formation of germinal centers and maintenance of the humoral response is discussed.