ADMINISTRATION OF ANTI-CD45 MAB SPECIFIC FOR A B-CELL-RESTRICTED EPITOPE ABROGATES THE B-CELL RESPONSE TO A T-DEPENDENT ANTIGEN IN-VIVO

CD45 is a receptor-like protein tyrosine phosphatase expressed exclusi vely by cells of the hemopoietic lineage. Studies in vitro involving t reatment of B cells with anti-CD45 mAb have demonstrated that ligand b inding to CD45 alters the cell's response to various activation/differ entiation stimuli. In general anti-CD45 treatment has been shown to ex ert an inhibitory effect on early activation events resulting in the f ailure of quiescent B cells to enter the cell cycle. These studies sug gest that CD45 acts as an important regulatory molecule in vitro, that controls B cell function. In contrast, little is known concerning the role that CD45 plays in vivo regarding regulation of B cell activatio n and differentiation in response to T-dependent Ag. In our study the anti-CD45 mAb RA3.6B2, which recognizes a B cell-restricted epitope, w as used to examine this question. Administration of anti-CD45 mAb in v ivo was found to inhibit the proliferative response of splenocytes whe n stimulated with B cell-, but not T cell-specific mitogens. Immunizat ion with the T-dependent Ag FITC-KLH in the presence of increasing amo unts of anti-CD45 mAb resulted in a significant, dose-dependent inhibi tion of the plaque-forming cell response. Additionally, anti-CD45 mAb inhibited the production of FITC-specific serum antibodies indicating that the effect was systemic. Finally, anti-CD45 mAb appeared to exert a maximal effect at earlier time points, within 48 h of Ag administra tion, suggesting that B cell activation was primarily affected. These results provide evidence to support the conclusion that CD45 is an imp ortant regulatory molecule that is involved in the control of B cell a ctivation in vivo.