Multiple immunoglobulin heavy-chain gene transcripts in Abelson murine leukemia virus-transformed lymphoid cell lines.

Abstract

Lymphoid cells transformed by Abelson murine leukemia virus (A-MuLV) contain three classes of RNA transcripts from immunoglobulin mu genes. P mu-mRNAs (productive) correspond to the normal 2.7-kilobase (kb) membrane (mu m) and 2.4-kb secreted (mu s) mu mRNA species both in size and coding capacity and occur at approximately equal abundance in most mu-positive (pre-B-like) A-MuLV transformants. A mu-mRNAs (aberrant) generally fall into one of two categories--aberrantly small 2.3-kb mu m and 2.0-kb mu s mRNAs which encode aberrantly small mu polypeptide chains, or normal-sized, V H-containing mu RNAs which do not encode immunologically identifiable mu polypeptide chains. In one case, the latter type of A mu-mRNA was demonstrated to result from an in-phase termination codon in the D segment of the mu mRNA. Also, most, if not all, A-MuLV transformants express members of a 3.0 to 1.9-kb set of C mu-containing, but V H-negative S mu-RNAs (for sterile), the expression of which may occur simultaneously with but independently of P mu-mRNAs or A mu-mRNAs. The S mu-RNA sequences do not encode immunologically identifiable mu chains and can be produced by cells with unrearranged heavy-chain alleles, such as T-lymphocytes, although the structure of the S mu-RNAs from T-lymphoid cells appears to be different from that of B-lymphoid cell S mu-RNAs. Certain A-MuLV transformants also express gamma-RNA sequences that are probably analogous to the three different forms of mu RNA. These data support the concept that heavy-chain allelic exclusion, like that of light chains, is not mediated by control at the DNA or RNA levels but is probably a consequence of feedback control from cytoplasmic mu chains.

Truncated mu (mu') chains in murine IgM. Evidence that mu' chains lack variable regions.

“…This is consistent with previous findings (33) indicating that Su-RNA in the 70Z/3, 38C-13, and C2 cell lines have different possible initiation sites, one of which is located ~0.3 kb upstream of the DQ52 gene segment. Also, Stt-RNA show the same regulated termination at tts or #m polyadenylation sites as do productive #-mRNA (33,49,51). In the case of the C2 cell line, all the S# RNA terminate at the tts site (33), consistent with the idea that #'(53) corresponds to an incompletely glycosylated #'s chain.…”

“…Various sizes of Stt-RNA, 1.9-3.0 kb, have been reported in pre-B, B, T, and other cell types (33,(49)(50)(51). S#-RNA occur independently of productive # mRNA (49) and may originate from unrearranged tt loci (51).…”

Murine lambda gene rearrangements: the stochastic model prevails over the ordered model.

“…The H chain genes rearrange first, followed by the light ones (H -L). Furthermore, the expressed membranebound form of /A chain (um) which signals cessation of H chain locus rearrangement has been shown to activate rearrangement of the x locus (Alt et al, 1982;Alt et al, 1984;Reth et al, 1985;Iglesias et al, 1987;Nussenzweig et al, 1987;Reth et al, 1987;Mantz et al, 1988), thus cumulating positive and negative functions. With respect to the x/X isotypic exclusion, there is a considerable body of evidence for an ordered regulated model in which x is ( Oxford University Press expressed before X (x -X).…”

Pro-B cells sense productive immunoglobulin heavy chain rearrangement irrespective of polypeptide production

“…In the genetic regulation model of H chain allelic exclusion, μH chain protein (as part of the pre-BCR) inhibits further rearrangements at the IgH locus, so that a second, functional IgH gene cannot be assembled (18). However, how is this inhibition accomplished?…”