Extensive splenic B cell activation in IgM-transgenic mice.

Two lines of IgM-transgenic mice were analyzed for the state of activation of their splenic compartment, with regard to the frequency of large cells in the different lymphoid subpopulations, and to the isotype distribution of background plasma cells. We observed an extensive B cell activation preferentially involving B lymphocytes co-expressing transgenic and endogenous IgM (IgD), and resulting in massive immunoglobulin class switch. Nearly all splenic plasma cells contain endogenous immunoglobulins, with frequencies of IgG and IgA plasma cells significantly higher than in normal mice. There are virtually no plasma cells that produce only the transgenic IgM. Moreover, only a proportion of plasma cells producing endogenous immunoglobulins co-express the transgenic product. In addition to these observations that apply to both transgenic lines, differences were found between the two lines concerning the quantitative expression of the transgenic IgM, the frequency of cells expressing the transgene and the magnitude of switch. These data are indicative of the complexity of the IgM-transgenic mouse model, in which the phenomenology may depend on the transgene insertional position, on B cell physiology and on immunological mechanisms of recognition, induction and regulation.