SIGNALING VIA MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II MOLECULES ANDANTIGEN RECEPTORS ENHANCES THE B-CELL RESPONSE TO GP39 CD40 LIGAND/

Activated T cells induce proliferation and differentiation of resting B cells in vitro through their CD40 molecules and lymphokine receptors . However, despite constitutive B cell expression of CD40 and lymphoki ne receptors, widespread nonspecific polyclonal B cell activation by a ctivated T cells is seldom observed in vivo. The present study was des igned to test the hypothesis that signals delivered via the B cell ant igen (Ag) receptor (membrane immunoglobulin, mIg) and major histocompa tibility complex (MHC) class II molecules enhance B cell responsivenes s to CD40-mediated signals, providing specificity to the Ag-nonspecifi c, MHC-unrestricted CD40 signal. To test this hypothesis, both an Ag-s pecific mouse B cell clone CH12.LX, and freshly isolated resting splen ic B cells were cultured with either soluble or membrane-bound forms o f the T cell ligand for CD40 (CD40L), in the presence or absence of ad ditional signals provided by Ag or anti-IgM, interleukin-4, and class II-specific monoclonal antibody (mAb). Differentiation of CH12.LX cell s and proliferation of splenic B cells in response to both forms of CD 40L was greatly enhanced by exposure to mig-mediated signals, with gre atest enhancement seen when cells were cultured with Ag prior to recei ving other signals. Response to CD40L was further enhanced by concurre nt culture with class II-specific, but not class I-specific mAb. Enhan cement was greatest at limiting concentrations of CD40L. The ability o f class II MHC-mediated signals to enhance Ag-specific B cell responsi veness to CD40-mediated signaling may selectively promote the activati on of B cell clones capable of cognate interactions with helper T cell s.