Open AccessLight chain inclusion permits terminal B cell differentiation and does not necessarily result in autoreactivity
Author(s) -
Christophe Sirac,
Claire Carrion,
Sophie Duchez,
Isabelle Comte,
Michel Cogné
Publication year - 2006
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0509121103
Subject(s) - immunoglobulin light chain , allelic exclusion , b cell , antibody , biology , mutant , microbiology and biotechnology , transgene , immunoglobulin class switching , gene rearrangement , cell , gene , genetics , t cell , t cell receptor , immune system
Mice in which the Jkappa cluster was replaced with a VkappaJkappa rearranged gene were studied. More than 90% of B cells from homozygous mutant mice expressed the transgenic kappa chain but showed a slightly reduced level of kappa 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 kappa 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 kappa/lambda 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.