B cell development in mice with a defective λ5 gene

The surrogate light chain encoded by the two pre‐B cell‐specific genes VpreB and λ5 plays a critical role in B cell development of the mouse. It has been shown that targeted disruption of the λ 5gene 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 (slg)+ 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 λ 5T/λ.5T 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 λ 5T/λ 5T 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 × 105 sIg+ B cells from the pre‐B‐I cell pool in the absence of a normal pool of pre‐B‐II cells.