VH gene replacement occurs in the spleen and bone marrow of non-autoimmune quasi-monoclonal mice
✍ Scribed by Fred E. Bertrand; Rachel Golub; Gillian E. Wu
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 158 KB
- Volume
- 28
- Category
- Article
- ISSN
- 0014-2980
No coin nor oath required. For personal study only.
✦ Synopsis
Genes encoding the heavy chain portion of immunoglobulin molecules arise from the combinatorial association of V, D and J gene segments, which occurs during discrete stages of B lineage development in the bone marrow. Recently, V H replacement, a form of receptor editing, has been described, in which the variable region of an existing VDJ H rearrangement is replaced by another V H gene segment in a recombination event believed to involve an embedded heptamer within the coding region of the V H . Studies of transgenic mice with "knocked-in" VDJ H genes encoding anti-DNA specificity have demonstrated that receptor editing of the heavy chain is one mechanism by which autoreactive B cell receptors can be modified. Another mouse, the "quasi-monoclonal", which encodes a "knocked-in" VDJ H for the hapten NP also contains B lineage cells that undergo V H replacement. This suggests that V H replacement may play a role in the normal diversification of the antibody repertoire. Using a ligation-mediated PCR assay, we have identified V QM double-stranded DNA breaks indicative of V H replacement intermediates from bone marrow and splenic B lineage cells of quasimonoclonal mice in the absence of immunization. V QM to J558 recombination deletion products consistent with V H replacement were also detected in both the bone marrow and spleen of non-immunized quasi-monoclonal mice. Moreover, RAG-1 transcripts were detected in the spleen. These data suggest that V H replacement can be part of the mechanism(s) used by B lineage cells to generate diversity throughout B lineage development, including later stages occurring in secondary lymphoid tissues.