Intrinsic binding of V genes to autoantigens may contribute to BCR repertoire

摘要

The B-cell to become mature requires constant stimulus throughout its development. This occurs in subsequent steps of signal transduction. Current viewpoints support that both a positive selection pressure for autoantigens and a tonic signaling constitutively stimulate B-cell maturation. We found evidence in this work that support that some variable genes have an intrinsic reactivity towards endogenous autoantigens. This was achieved by an analysis of the variable gene segment in its germline configuration, independent of VDJ recombination. The experiments were designed based on a search of a public antibody database, in which a mouse heavy variable gene segment was found to be over represented in anti-nucleic acid antibodies. We tested it for ssDNA binding in vitro using phage display technology to create libraries of peptides with high binding affinity to oligo deoxythimidine. A Bioinformatics pipeline was then performed to analyse the phage display libraries in a large scale, and the results showed that DNA binding is biased in the antibody by the VH gene segment. Two peptides of the complementary determining region were found to be overrepresented in the libraries were also investigated in detail. These findings give valuable input to contribute to the establishment of the immature B-cell repertoire.