kappa+lambda+ dual receptor B cells are present in the human peripheral repertoire.
It is a common notion that mature B lymphocytes express either kappa or lambda light (L) chains, although the mechanism that leads to such isotypic exclusion is still debated. We have investigated the extent of L chain isotypic exclusion in normal human peripheral blood B lymphocytes. By three-color staining with anti-CD19, anti-kappa, and anti-lambda antibodies we could estimate that 0.2-0.5% of peripheral blood B cells from healthy adults express both kappa and lambda on the cell surface. The kappa+lambda+ cells were sorted, immortalized by Epstein-Barr virus, and five independent clones were characterized in detail. All clones express both kappa and lambda on the cell surface and produce immunoglobulin M that contain both kappa and lambda chains in the same molecule, i.e., hybrid antibodies. Sequencing of the L chains revealed in three out of five clones evidence for somatic mutations. It is interesting to note that among a panel of single receptor B cell clones we identified two lambda+ clones that carried a productively rearranged kappa, which was inactivated by a stop codon generated by somatic mutation. These findings indicate that dual receptor B lymphocytes can be found among mature antigen-selected B cells and suggest that somatic mutation can contribute to increase the degree of isotypic exclusion by inactivating a passenger, nonselected L chain.
Giachino
C
C
Basel Institute for Immunology, Switzerland.
Padovan
E
E
Lanzavecchia
A
A
D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D005803:Genes, Immunoglobulin; D006801:Humans; D007075:Immunoglobulin M / Q000096:biosynthesis; D007145:Immunoglobulin kappa-Chains / Q000032:analysis* / Q000235:genetics; D007146:Immunoglobulin lambda-Chains / Q000032:analysis*; D008969:Molecular Sequence Data; D009154:Mutation
D007075:Immunoglobulin M; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains