Immunoglobulin gene rearrangement in B cell deficient mice generated by targeted deletion of the JH locus

B lymphocyte differentiation is characterized by an orderedseries of Ig gene assembly and expression events. In the majorityof normal B cells, assembly and expression of Ig heavy (H) chaingenes precedes that of light (L) chain genes. To determine therole of the Ig heavy chain protein in B cell development andL chain gene rearrangement, we have generated mice that cannotassemble Ig H chain genes as a result of targeted deletion ofthe J_H gene segments in embryonic stem cells. Mice homozygousfor this deletion are devoid of slg⁺ B cells in the bone marrowand periphery. B cell differentiation in these mice is blockedat the large, CD43⁺ precursor stage. However, these precursorB cells do assemble L chain genes at a low level in the absenceof µ H chain proteins. These data demonstrate that rearrangementand expression of the µ H chain gene is not absolutelyrequired for L chain gene rearrangement in vivo. Expressionof µ chains may facilitate either efficient L chain generearrangement or the survival of cells that have rearrangedlight chain genes by promoting the differentiation of large,CD43⁺ to small, CD43^– pre-B cells.