Gamma 2b transgenic mice as a model for the role of immunoglobulins in B cell development

Abstract

The development of B lymphocytes is tightly linked to the expression of immunoglobulins (Igs). Pro/preB cells which do not correctly rearrange heavy/light chain genes are aborted. Correctly rearranged Ig transgenes are apparently recognized by the developing B cells and can prevent the rearrangement of endogenous Ig genes. Both mu and gamma 2b heavy chain genes cause this feedback inhibition of heavy chain gene rearrangement. Mu transgenes can in addition replace endogenous MU in its preB cell survival/maturation function. However, several different transgenic lines have shown that gamma 2b transgenes do not provide the nurturing functions of mu, except for one unique gamma 2b transgenic line, the C line. In this line mature B cells express gamma 2b only. Presumably, an unknown gene has been activated at the transgene integration site whose product overcomes the need for mu. The function of this gene depends of the presence of the surrogate light chain (sL), and thus must operate in combination with the preB cell receptor or in a downstream signaling/antiapoptosis event requiring the gamma 2b/sL receptor. The analysis of the two types of gamma 2b transgenic mice shows that the signals for preB cell development are highly complex and promises to reveal new insights into the molecular and cellular mechanisms of B cell maturation.