D-H ELEMENT READING FRAME SELECTION IS INFLUENCED BY AN IG HEAVY-CHAIN TRANSGENE, BUT NOT BY BCL-2
- Author(s)
- Tarlinton, D; Strasser, A; McLean, M; Basten, A;
- Details
- Publication Year 1995-04-01,Volume 154,Issue #7,Page 3341-3350
- Journal Title
- JOURNAL OF IMMUNOLOGY
- Publication Type
- Journal Article
- Abstract
- Mouse B cell precursors containing Ig D(H)J(H) junctions in one particular reading frame are selectively lost during B cell development. In this register, arbitrarily referred to as reading frame 2, D(H)J(H) junctions give rise to an open reading frame starting upstream of the D-H element and including the D(H)J(H)-peptide fused to the constant region of IgM. Expression of this protein, called D mu, has been strongly implicated in the loss of B cell precursors containing reading frame 2 D(H)J(H) junctions. In an attempt to elucidate the means of D mu counterselection, we have examined the reading frame distribution of D(H)J(H) junctions in peripheral B cells from mice transgenic for either the human bcl-2 oncogene or for a functionally rearranged Ig mu heavy chain. In bcl-2 transgenic mice, reading frame 2 accounted for <5% of the D(H)J(H) junctions in peripheral B cells, a value not significantly different from controls. Reading frames 1 and 3 were equally represented among the remaining junctions. By contrast, the reading frame distribution of endogenous D(H)J(H) junctions in splenic B cells from Ig mu heavy chain transgenic mice showed no evidence of bias against D mu encoding D(H)J(H) junctions. Reading frames 2 and 3 accounted for 27% and 30% of the sequenced D(H)J(H) junctions, respectively, and the remaining 43% were reading frame 1. Thus although the presence of BCL-2 cannot prevent the selective loss of reading frame 2 D(H)J(H) B cells, a functional mu heavy chain can. These results suggest that D mu-expressing B cell precursors may be selectively lost because of the premature and inappropriate cessation of heavy chain gene rearrangement rather than because of the induction of an apoptotic process which can be blocked by BCL-2.
- Publisher
- AMER ASSOC IMMUNOLOGISTS
- Keywords
- B-CELL DEVELOPMENT; IMMUNOGLOBULIN GENE REARRANGEMENT; MOUSE BONE-MARROW; D-MU PROTEIN; ANTIBODY DIVERSITY; LYMPHOID-CELLS; EXPRESSION; MICE; DEATH; DIFFERENTIATION
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Creation Date: 1995-04-01 12:00:00