First Author | Nakajima PB | Year | 2009 |
Journal | J Immunol | Volume | 182 |
Issue | 6 | Pages | 3583-96 |
PubMed ID | 19265137 | Mgi Jnum | J:244234 |
Mgi Id | MGI:5913013 | Doi | 10.4049/jimmunol.0802533 |
Citation | Nakajima PB, et al. (2009) Two distinct populations of H chain-edited B cells show differential surrogate L chain dependence. J Immunol 182(6):3583-96 |
abstractText | Developing autoreactive B cells may edit (change) their specificity by secondary H or L chain gene rearrangement. Recently, using mice hemizygous for a site-directed VDJH and VJkappa transgene (tg) encoding an autoreactive Ab, we reported ongoing L chain editing not only in bone marrow cells with a pre-B/immature B cell phenotype but also in immature/transitional splenic B cells. Using the same transgenic model, we report here that editing at the H chain locus appears to occur exclusively in bone marrow cells with a pro-B phenotype. H chain editing is shown to involve VH replacement at the tg allele or VH rearrangement at the wild-type (wt) allele when the tg is inactivated by nonproductive VH replacement. VH replacement/rearrangement at the tg/wt alleles was found to entail diverse usage of VH genes. Whereas the development of edited B cells expressing the wt allele was dependent on the lambda5 component of the surrogate L chain, the development of B cells expressing the tg allele, including those with VH replacement, appeared to be lambda5 independent. We suggest that the unique CDR3 region of the tg-encoded muH chain is responsible for the lambda5 independence of tg-expressing B cells. |