Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 238K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Chang, Y. Articles by Bosma, G. C. Search for Related Content PubMed PubMed Citation Articles by Chang, Y. Articles by Bosma, G. C. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Social Bookmarking                            What's this?

Articles

Yung Chang^*,, Melvin J. Bosma^*, and Gayle C. Bosma^*

From the ^* Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111; and the Department of Microbiology, Arizona State University, Tempe, Arizona 85287

Here we show that suppression of VH–DJH rearrangement in mice bearing a µ heavy (H) chain transgene (µ-tg mice) is associated with an extended period of DH–JH rearrangement, the first step of Immunoglobulin H chain gene rearrangement. Whereas DH–JH rearrangement is normally initiated and completed at the pro-B cell stage, in µ-tg mice it continues beyond this stage and occurs most frequently at the small (late) pre-B stage. Despite ongoing DH–JH rearrangement in late pre-B cells of µ-tg mice, VH–DJH rearrangement is not detectable in these cells. We infer that the lack of VH–DJH rearrangement primarily reflects tg-induced acceleration of B cell differentiation past the stage at which rearrangement of VH elements is permissible. In support of this inference, we find that the normal representation of early B lineage subsets is markedly altered in µ-tg mice. We suggest that the effect of a productive VH–DJH rearrangement at an endogenous H chain allele may be similar to that of a µ-tg; i.e., cells that make a productive VH–DJH rearrangement on the first attempt rapidly progress to a developmental stage that precludes VH–DJH rearrangement at the other allele (allelic exclusion).

Key Words: V(D)J rearrangement • immunoglobulin transgenic mice • B cell differentiation • allelic exclusion

Dr. Chang's current address is Arizona State University, Department of Microbiology, Tempe, AZ 85287.

² The extent to which RAG expression is upregulated earlier in subsets B and B' of µ-tg mice is not known. If RAG expression is not fully upregulated in these subsets, this could also contribute to the observed lower level of DH–JH rearrangement in the pro-B (B220⁺CD43⁺) versus the late pre-B (B220⁺CD43^–) cell fraction of µ-tg mice (see Fig. 4).

Abbreviations used: BCR, B cell receptor; DSB, double strand break; HSA, heat stable antigen; LM-PCR, ligation-mediated PCR; RAG, recombinase activation gene; tg, transgene.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS