GAMMA-2B TRANSGENIC MICE AS A MODEL FOR THE ROLE OF IMMUNOGLOBULINS IN B-CELL DEVELOPMENT

The development of B lymphocytes is tightly linked to the expression o f immunoglobulins (Igs). Pro/preB cells which do not correctly rearran ge heavy/light chain genes are aborted. Correctly rearranged Ig transg enes are apparently recognized by the developing B cells and can preve nt the rearrangement of endogenous Ig genes. Both mu and gamma 2b heav y chain genes cause this feedback inhibition of heavy chain gene rearr angement. mu transgenes can in addition replace endogenous mu in its p reB cell survival/maturation function. However, several different tran sgenic lines have shown that gamma 2b transgenes do not provide the nu rturing functions of mu, except for one unique gamma 2b transgenic lin e, the C line. In this line mature B cells express gamma 2b only. Pres umably, an unknown gene has been activated at the transgene integratio n site whose product overcomes the need for mu. The function of this g ene depends of the presence of the surrogate light chain (st), and thu s must operate in combination with the preB cell receptor or in a down stream signaling/antiapoptosis event requiring the gamma 2b/sL recepto r. The analysis of the two types of gamma 2b transgenic mice shows tha t the signals for preB cell development are highly complex and promise s to reveal new insights into the molecular and cellular mechanisms of B cell maturation.