Light chain inclusion permits terminal B cell differentiation and does not necessarily result in autoreactivity

Mice in which the Jκ cluster was replaced with a VκJκ rearranged gene were studied. More than 90% of B cells from homozygous mutant mice expressed the transgenic κ chain but showed a slightly reduced level of κ transcripts compared with WT B lymphocytes. Light chain inclusion was apparent in 10% of B cells from these mice and raised 25% in hemizygous mice with a still lower expression of the knockin κ chain. Beyond the rules of clonal selection, peripheral B cells developed in such animals, with included cells being activated and differentiating into class-switched or antibody-secreting cells. The high amount of included mature B cells was associated with an increase of hybrid κ/λ immunoglobulins but not with the increased prevalence of autoantibodies. Altogether, these data suggest that light chain exclusion prevalent in normal B cells mostly results from ordered rearrangements and stochastic mechanisms but is neither tightly ensured by a stringent cell selection process nor absolutely required for normal B cell function.

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