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Extensive Junctional Diversity in Ig Light Chain Genes from Early B Cell Progenitors of µMT Mice¹

Laurent A. Bentolila^*, Stacy Olson, Aaron Marshall, François Rougeon^*, Christopher J. Paige, Noëlle Doyen^* and Gillian E. Wu^2,

^* Unité de Génétique et Biochimie du Développement, Unité de Recherche Associée, Centre National de la Recherche Scientifique 1960, Département d’Immunologie, Institut Pasteur, Paris, France; and Department of Immunology, University of Toronto, and Ontario Cancer Institute, Toronto, Canada

Nontemplated (N) nucleotide additions contribute significantly to the junctional diversity of all Ag receptor chains in adult mice except Ig light (L) chains, primarily because terminal deoxynucleotidyl transferase (TdT) expression is turned off at the time of their rearrangement in pre-B cells. However, because some Ig L chain gene rearrangements are detectable earlier during B cell ontogeny when TdT expression is thought to be maximal, we have examined the junctional processing of - and -chain genes of CD45(B220)⁺CD43⁺ pro-B cells from µMT mice. We found that both and coding junctions formed in these B cell precursors were extensively diversified with N-region additions. Together, these findings demonstrate that Ig L chain genes are equally accessible to TdT in pro-B cells as Ig heavy chain genes. Surprisingly, however, the two L chain isotypes differed in the pattern of N addition, which was more prevalent at the -chain locus. We observed the same diversity pattern in pre-B cells from TdT-transgenic mice. These results suggest that some aspects of TdT processing could be influenced by factors intrinsic to the sequence of Ig genes and/or the process of V(D)J recombination itself.