B-CELL DEVELOPMENT IN MICE WITH A DEFECTIVE LAMBDA-5 GENE

The surrogate light chain encoded by the two pre-B cell-specific genes V(preB) and lambda5 plays a critical role in B cell development of th e mouse. It has been shown that targeted disruption of the lambda5 gen e 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 imm unoglobulin (sIg)+ B cells in the periphery. In this report we show th at D(H)J(H)-rearranged B220- and B220+, CD43+, c-kit+, sIgM- pro- and pre-B-1 cells with long-term capacity to proliferate in vitro on strom al cells in the presence of interleukin-7 are present in normal number s in the bone marrow of lambda5T/lambda5T mice at various ages. They e xpress normal levels Of V(preB) mRNA but, in contrast to normal pre-B- 1 cells, do not express surrogate light chain on their surface. Pre-B- 1 cells from fetal liver and bone marrow of lambda5T/lambda5T mice dif ferentiate 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- c ells could be accounted for by the daily production of approximately 5 X 10(5) sIg+ B cells from the pre-B-1 cell pool in the absence of a n ormal pool of pre-B-H cells.