Gene conversion events contribute to the polymorphic variation of the surrogate light chain gene lambda 5/14.1.

Normally occurring and experimentally induced models of immunodeficiency indicate that B cell development and antibody production are influenced by genetic factors. It is highly likely that polymorphic variants in genes that encode receptors for growth and differentiation factors, signal transduction molecules, and components of the B cell and pre-B-cell receptor complex contribute to this genetic control. We have identified a surprisingly large number of polymorphic variants in lambda5/14.1. Together with VpreB, lambda5/14.1 forms the surrogate light chain in the pre-B-cell receptor complex. Thirteen variant alleles of lambda5/14.1 were found in 134 unrelated individuals. Nine of these variants result in changes in the amino acid sequence of this small protein. The majority of the single base pair substitutions in lambda5/14.1 could be attributed to gene conversion events in which donor sequences from the lambda5 pseudogenes, 16.1, 16.2, and Glambda1, replace the wild-type sequence in the lambda5/14.1 functional gene. These findings indicate that gene conversion events play a major role in generating diversity that could affect stability or expression of the pre-B-cell receptor complex.