Regulation of immunoglobulin light chain gene rearrangements during early B cell development in the human

Southern blot analyses of immunoglobulin light chain gene rearrangements in human leukemias and myelomas indicated that λ loci in κ-producing cells are largely unrearranged while κ loci in λ producers are often rearranged and inactivated by rearrangements of the kappa-deleting element (KDE). For a systematic analysis of the regulation of light chain rearrangements during early B cell development in normal human B cells also considering functionality of the rearrangements, we used FACS-sorted single naive κ- and λ-expressing B cells from peripheral blood of healthy humans. VκJκ and VλJλ joints and rearrangements involving the KDE were amplified simultaneously from single cells and sequenced. Whereas only 2 – 3 % of κ-expressing cells cary Vλ Jλ joints, nearly all λ-expressing cells have rearranged κ loci and indeed carry VκJκ joints. The VκJκ joints in λ-expressing cells exhibit preferential Jκ4 and Jκ5 over Jκ1 and Jκ2 usage compared to κ-expressing cells. Thirty percent of the VκJκ joints in λ producers are rearranged in-frame. These data indicateextensive sequential Vκ-Jκ rearrangements and inactivation of functional VκJκ joints in λ-expressing cells, presumably before VλJλ joining.