Showing papers by "Mark M. Davis published in 1980"
TL;DR: It is shown that both μ m and μ s mRNAs are produced from transcripts of a single μ gene, suggesting that developmental control of the site at which poly(A) is added to transcripts of the μ gene determines the relative levels of μ m or μ s chain synthesis.
777 citations
TL;DR: A model for variable region gene rearrangement mediated by proteins which recognize the same conserved sequences adjacent to both light and heavy chain immunoglobulin gene segments is proposed.
736 citations
TL;DR: The events of B-cell differentiation can be reconstructed in part through an analysis of the organisation of heavy-chain gene segments in differentiated B cells.
Abstract: The events of B-cell differentiation can be reconstructed in part through an analysis of the organisation of heavy-chain gene segments in differentiated B cells. A mouse immunoglobulin α heavy-chain gene is composed of at least three noncontiguous germ-line DNA segments—a VH gene segment, a JH gene segment associated with the Cμ gene segment, and the Cα gene segment. These gene segments are joined together by two distinct types of DNA rearrangements—a V–J joining and a CH switch.
249 citations
TL;DR: The lack of homology between this C alpha sequence and sequences reported for the C gamma 1 and C gamma 2b switch sites suggests that heavy chain switching is mediated by class-specific recognition sequences and, presumably, class- specific regulatory mechanisms.
Abstract: Immunoglobulin class switching involves specific DNA rearrangements of the gene segments coding for heavy chain constant regions (C_H) during B lymphocyte differentiation. In two different cases of C_µ to Cɑ switching examined here (T15 and M603) and one taken from the literature (MC101), three different sites on the 5' side of C_µ and three different sites on the 5' side of C_ɑ are joined together in the process of C_H switching. The sequences surrounding the three germ-line C_ɑ sites of recombination are highly conserved blocks of 30 nucleotides that may serve as recognition sequences for C_H switching to the C_ɑ gene. This putative recognition sequence is repeated 17 times in approximately 1400 nucleotides of the germ-line C_ɑ 5' flanking sequence. The lack of homology between this C_ɑ sequence and sequences reported for the C_(y1) and C_(y2b) switch sites suggests that heavy chain switching is mediated by class-specific recognition sequences and, presumably, class-specific regulatory mechanisms. In addition, it appears that in one example (MC101) C_H switching progressed from C_µ to C_ɑ to C_(y1). This switching pathway may present difficulties for the simple deletional model of C_H switching.
194 citations
TL;DR: The data support the hypothesis that expression of B-cell joining and C gene segments is unnecessary for T- cell helper and T-cell killer activity.
Abstract: We have analyzed four kinds of T cells for rearrangement and expression of immunoglobulin genes. These cells include: (a) whole thymus; (b) WEHI-22, a T-cell lymphoma; (c) HT-1, an major histocompatibility complex-restricted T helper line; and (d) CTLLi6, an H-2 alloreactive killer cell line. None of the B-cell joining and constant gene segments are rearranged in the T cells. The monoclonal cells do not express any C kappa, C lambda, Cmu or C alpha RNA species. Small amounts of C kappa, C alpha, and Cmu sequences are present in RNA prepared from the thymus, although the significance of this RNA for T-cell antigen receptor synthesis is uncertain. The data support the hypothesis that expression of B-cell joining and C gene segments is unnecessary for T-cell helper and T-cell killer activity.
71 citations
54 citations
TL;DR: It is demonstrated here that intervening DNA sequences separate each of the four coding regions for Cμ domains, and that the coding areas for the Cμ4 domain and the C-terminal tail are directly contiguous.
Abstract: The IgM molecule is composed of subunits made up of two light chain and two heavy chain (mu) polypeptides. The mu chain is encoded by several gene segments--variable (V), joining (J) and constant (Cmu). The Cmu gene segment is of particular interest for several reasons. First, the mu chain must exist in two very different environments--as an integral membrane protein in receptor IgM molecules (micrometer) and as soluble serum protein in IgM molecules into the blood (mus). Second, the Cmu region in mus is composed of four homology units or domains (Cmu1, Cmu2, Cmu3 and Cmu4) of approximately 110 amino acid residues plus a C-terminal tail of 19 residues. We asked two questions concerning the organisation of the Cmu gene segment. (1) Are the homology units separated by intervening DNA sequences as has been reported for alpha (ref. 5), gamma 1 (ref. 6) and gamma 2b (ref. 7) heavy chain genes? (2) Is the C-terminal tail separated from the Cmu4 domain by an intervening DNA sequence? If so, DNA rearrangements or RNA splicing could generate hydrophilic and hydrophobic C-terminal tails for the mus and micrometer polypeptides, respectively. We demonstrate here that intervening DNA sequences separate each of the four coding regions for Cmu domains, and that the coding regions for the Cmu4 domains and the C-terminal tail are directly contiguous.
53 citations