Regulation of immunoglobulin production by nerve growth factor: Comparison with anti-CD40

Nerve growth factor (NGF) is a well-known neurotrophic factor acting on both the peripheral and the central nervous systems. In addition, it has been shown to play a role in the function of the immune system through specific receptors. The low-affinity NGF receptor (NGFR) is present on human B lymphocytes and has been shown to have structural homology with another specific B cell surface molecule, CD40. NGF and anti-CD40 have been shown to modulate B-cell proliferation and Immunoglobulin (Ig) secretion. However, there have been no studies directly comparing the properties of these putative B-cell growth factors, particularly similarities in receptor expression or their role in B cell function. In this study, we examined the expression of NGFR and CD40 in a number of B-lymphoblastoid cell lines, representative of various stages of differentiation. We found that NGFR and CD40 are expressed on all B-cell lines to various degrees with the exception of plasma cells. Using two Ig secreting cell lines, both NGF and anti-CD40 decreased Ig secretion in a dose-dependent manner. The interaction of NGF and anti-CD40 with interleukin-4 (IL-4) was surprisingly different. Whereas, IL-4 reversed the inhibitory effect of NGF on Ig secretion, it did not reverse that of anti-CD40. In addition, differences were observed at the level of receptor expression; IL-4 decreased the expression of NGFR, but increased that of CD40. These data indicate that although NGFR and CD40 are expressed in a co-ordinate fashion on B cells and exert similar effects on Ig secretion, differences in interaction with other growth factors may be important in their activities at different stages of B-cell differentiation.