COMPARING MACROPHAGES AND DENDRITIC LEUKOCYTES AS ANTIGEN-PRESENTING CELLS FOR HUMORAL RESPONSES IN-VIVO BY ANTIGEN TARGETING

Immunotargeting is a novel technique whereby antigen is directed again st antigen-presenting cells (APC) by conjugation to specific monoclona l antibodies (mAb). In this study we have employed the technique to in vestigate the efficiency of macrophages as APC compared with constitut ively major histocompatibility complex (MHC) class II-positive cells, i.e. dendritic leukocytes and B cells, in vivo. We first studied the o rgan retention of the radiolabeled conjugates by gamma counting, and t heir distribution within the draining lymph nodes by autoradiography. We could confirm that the conjugates reached the cells at which they w ere aimed. We then measured primary and secondary humoral responses. T he results confirmed previous findings that targeting with mAb against MHC class II, i.e. to dendritic leukocytes, strongly enhanced the pri mary humoral response. In contrast, anti-IgD conjugates, directed agai nst B cells Save only weak primary responses. Although conjugates dire cted against macrophages were retained for a longer time than the othe r conjugates, the primary humoral response was virtually abolished. Th e secondary responses, however, were at least as strong as those obtai ned in animals primed with control conjugates, whereas animals primed with anti-MHC class II conjugates showed little if any amplification o f the secondary response. The discrepancies between the various conjug ates could not be ascribed to T(H)1 versus T(H)2 responses as IgG1, Ig G2a, IgG2b and IgE titers all co-varied in single animals. A possible explanation for the observed results is that macrophages fail to induc e cytokine production for terminal differentiation of B cells to plasm a cells, whereas conversely, upon presentation by dendritic leukocytes most stimulated B cells mature to plasma cells, leaving less progeny for immunological memory