B cell development in mice with a defective lambda 5 gene.

Abstract

The surrogate light chain encoded by the two pre-B cell-specific genes VpreB and lambda 5 plays a critical role in B cell development of the mouse. It has been shown that targeted disruption of the lambda 5 gene results in a depletion of B220+ CD43- IgM-pre-B cells in bone marrow, and in a delayed appearance both of CD5+ as well as CD5- surface immunoglobulin (sIg)+ B cells in the periphery. In this report we show that DHJH-rearranged B220- and B220+, CD43+, c-kit+, sIgM- pro- and pre-B-I cells with long-term capacity to proliferate in vitro on stromal cells in the presence of interleukin-7 are present in normal numbers in the bone marrow of lambda 5 T/lambda 5 T mice at various ages. They express normal levels of VpreB mRNA but, in contrast to normal pre-B-I cells, do not express surrogate light chain on their surface. Pre-B-I cells from fetal liver and bone marrow of lambda 5 T/lambda 5 T mice differentiate with normal kinetics and in normal numbers to sIg+, mitogen-reactive B cells. These results suggest that the delayed generation of sIg+ B cells in the peripheral, mature compartments of CD5+ and CD5- cells could be accounted for by the daily production of approximately 5 x 10(5) sIg+ B cells from the pre-B-I cell pool in the absence of a normal pool of pre-B-II cells.