Analysis of heavy and light chain pairings indicates that receptor editing shapes the human antibody repertoire

RMT De Wildt, RMA Hoet, WJ van Venrooij… - Journal of molecular …, 1999 - Elsevier
RMT De Wildt, RMA Hoet, WJ van Venrooij, IM Tomlinson, G Winter
Journal of molecular biology, 1999Elsevier
In the bone marrow, diversity in the primary antibody repertoire is created by the
combinatorial rearrangement of different gene segments and by the association of different
heavy and light chains. During the secondary response in the germinal centres, antibodies
are diversified by somatic mutation and possibly by further rearrangements, or “receptor
editing”. Here, we have analysed the pairings of heavy and light chain variable domains
(VHand VL) in 365 human IgG+ B cells from peripheral blood, and established that these …
In the bone marrow, diversity in the primary antibody repertoire is created by the combinatorial rearrangement of different gene segments and by the association of different heavy and light chains. During the secondary response in the germinal centres, antibodies are diversified by somatic mutation and possibly by further rearrangements, or “receptor editing”. Here, we have analysed the pairings of heavy and light chain variable domains (VHand VL) in 365 human IgG+B cells from peripheral blood, and established that these pairings are largely random. The repertoire is dominated by a limited number of pairings of segments and folds. Among these pairings we identified two identical mutated heavy chains in combination with two different mutated light chains (one kappa and one lambda). This shows that receptor editing occurs in the human periphery and that the same antibody lineage can be subjected to both receptor editing and somatic hypermutation. This suggests that receptor editing may be used together with somatic mutation for the affinity maturation of antibodies. We also propose that receptor editing has shaped variable gene segment use and the evolution of V gene families.
Elsevier