LAMBDA-5, BUT NOT MU, IS REQUIRED FOR B-CELL MATURATION IN A UNIQUE GAMMA-2B TRANSGENIC MOUSE LINE

gamma 2b transgenic mice have a severe B cell defect, apparently cause d by strong feedback inhibition of endogenous H-gene rearrangement cou pled with an inability of gamma 2b to provide the sunival/maturation f unctions of mu. A unique gamma 2b transgenic line, named the C line, w as found to permit B cell development. When the C line is crossed with a mu-membrane knockout line, gamma 2b(+) B cells develop in the homoz ygous knockout. In contrast, a transgenic line representative of all t he other gamma 2b lines is completely B cell deficient when CL-mem is deleted. Strikingly, the C phenotype is dominant in C x other gamma 2b transgenic line crosses. There is no evidence for higher gamma 2b tra nsgene expression or other position effects on the transgene in the C mouse. The sequences of the three gamma 2b transgene copies in the C l ine are identical to that of the original transgene. These results hav e led to the conclusion that in the C line the transgene integration c onstitutively induces a gene whose expression can replace mu. To more clearly delineate the stage at which the altered phenotype of the C li ne is expressed, C mice were crossed onto a lambda 5 knockout backgrou nd. In the absence of lambda 5, the C line produces no B cells. Since it was also found that gamma 2b can associate with the surrogate light chain (sL; lambda 5/Vpre-B), the crosses between C line gamma 2b mice and lambda 5 knockout mice suggest that gamma 2b/sL is required for B cell maturation in this mouse line. Thus, gamma 2b alone is unable to replace mu for pre-B cell survival/maturation; however, in combinatio n with an unknown factor and the st, gamma 2b can provide these nurtur ing functions.