Inappropriate expression of IgD from a transgene inhibits the function of antigen-specific memory B cells

IgD expression has been shown to be downmodulated upon mitogenic or antigen ic activation of B cells. To investigate whether this decrease is of functi onal significance we studied a mouse strain that expresses transgenic IgD o n all B cells. The rearranged gene encoding the heavy chain of this IgD req uires endogenous gene rearrangement before it can be expressed; therefore, normal B cell development is not affected. As a result, both transgenic IgD and endogenous IgM and IgD are expressed on all peripheral B cells. We sho w that the presence of extraneous IgD does not affect normal B cell activat ion by polyclonal stimulators, nor does it affect the primary IgM or IgG re sponses to TI or TD antigens. However, the secondary memory response is sig nificantly diminished. The decrease is not attributable to a defective gene ration of memory B cells; instead the activation of memory cells appears to be compromised. Since the depressed response can be overcome by prior aggr egation of the transgenic IgD with allotype-specific anti-IgD antibodies, i t appears that persistence of the transgenic IgD on memory cells may influe nce their ability to be activated. Thus, the decrease in IgD expression on normal B cells after activation may be necessary for optimal activation of memory cells. (C) 2001 Academic Press.