Control of Expression of Immunoglobulin Genes

Storb, Ursula; Engler, Peter; Hagman, James; Gollahon, Katherine A.; Manz, J; Roth, Patricia; Rudin, C; Doglio, Lynn; Hackett, Jr J; Haasch, Deanna L.; Chaplin, David; Lo, David; Brinster, Ralph L.

doi:10.1007/978-3-642-83755-5_42

Cited by 13 publications

(16 citation statements)

References 30 publications

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“…Recently, a series of studies has been published using transgenic mice carrying a functionally rearranged ,u heavy chain gene to test this hypothesis (6)(7)(8)(9)(10)(11). Data from these studies have generally appeared consistent with the overall hypothesis; however, it is difficult to draw a firm conclusion from the evidence presented.…”

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confidence: 99%

“…Data from these studies have generally appeared consistent with the overall hypothesis; however, it is difficult to draw a firm conclusion from the evidence presented. Three potential problems cloud interpretation of these data: (i) in most of the previous studies, the expression of transgenic and endogenous IgM in individual B cells was primarily determined by analysis of cell lines (Abelson transformed lines or hybridomas) derived from the transgenic mice and are not necessarily representative of the B-cell populations actually present in the animals (7-11); (ii) several of the transgenic lines studied were made with outbred (F1) founder mice (6,(8)(9)(10) and, thus, will have considerable genetic variability, which may affect B-cell development; and (iii) our recent studies (with the M54 and M95 inbred transgenic mouse strains) demonstrate that the introduction of the immunoglobulin transgene can selectively block development of B-cell subpopulations (12).…”

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confidence: 99%

“…The development of these lines has been described in detail (14). The transgenic ,234-4 mice were generously provided by U. Storb (University of Chicago) and R. Brinster (University of Pennsylvania) (9).…”

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confidence: 99%

“…For each analysis, data from 30,000 viable cells were collected. Data are presented as 5% probability contour maps (19 (9), which has a different ,u transgene construct than the one in M54 and M95. Proc.…”

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confidence: 99%

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Rearrangement and expression of endogenous immunoglobulin genes occur in many murine B cells expressing transgenic membrane IgM.

Stall

Kroese²,

Gadus³

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

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Transgenic mice carrying immunoglobulin genes coding for it heavy chain and K light chain have been used to study the mechanisms involved in allelic and isotypic exclusion. We report here that individual cells from transgenic mice carrying a functionally rearranged la heavy chain gene (capable of generating both membrane and secreted forms of IgM) can rearrange an endogenous ,u heavy chain gene and simultaneously produce both transgenic and endogenous IgM. These "double-producing" cells express both endogenous and transgenic IgM in the cytoplasm (detected by immunohistology) and on the cell surface (detected by multiparameter fluorescence-activated cell sorter analysis). In addition, they secrete mixed IgM molecules containing both transgenic and endogenous 1L heavy chains (detected in serum by radioimmune assay). The transgenic mice studied also have relatively large numbers of cells that produce endogenous immunoglobulin in the absence of detectable transgenic immunoglobulin ("endogenous-only cells"). The mechanisms that generate double-producing cells and endogenous-only cells appear to be under genetic control because the frequencies of these B-cell populations are characteristic for a given transgenic line. Thus, our frndings indicate that more is involved in triggering allelic exclusion than the simple presence or absence of membrane ja heavy chains (as has been previously postulated).

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confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Rearrangement and expression of endogenous immunoglobulin genes occur in many murine B cells expressing transgenic membrane IgM.

Stall

Kroese²,

Gadus³

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

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“…We are using our immunological probes to determine whether these two gene products are functioning as "light-chain surrogates" in pre-B cells and whether they encode the 16-and 22-kDa immunoglobulin ,u coprecipitated bands. There is mounting evidence that immunoglobulin heavychain allelic exclusion is mediated by a functionally rearranged immunoglobulin heavy-chain gene in pre-B cells, which shuts off further V to DJ recombination (D, diversity region) and allows light-chain gene rearrangement to begin (31)(32)(33)(34)(35). The formation of a A heavy-chain surrogate light chain(s) complex in pre-B cells may be an essential step in this process.…”

Section: Ctccmg T H V F G S G T Q L T V L S Q P K a T P S V T L F P Pmentioning

confidence: 99%

Immunoglobulin lambda light-chain-related genes 14.1 and 16.1 are expressed in pre-B cells and may encode the human immunoglobulin omega light-chain protein.

Hollis

Evans²,

Stafford-Hollis³

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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Expression of a novel type of immunoglobulin C_λ transcripts in human mature B lymphocytes producing χ light chains

Guglielmi

Davi

1991

Eur J Immunol

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Ordered rearrangement of immunoglobulin genes (heavy chain then kappa and eventually lambda genes) is observed during B lymphocyte ontogeny. Unexpectedly, we found that human mature B cells producing kappa chains and having germ-line lambda genes contain lambda mRNA consisting of an invariant 5' region (herein termed X) and of one of the classical C lambda exons. The X region of these transcripts originates from a unique exon located 5 kb upstream of the J-C lambda 1 gene segment. X-C lambda mRNA expression occurs without somatic DNA rearrangement. The use of the X DNA fragment as a probe allows definition of a family of human genes that comprises at least four members and includes the first exon of the lambda 14.1 gene. The latter is selectively transcribed in pre-B lymphocytes and directs the synthesis of a lambda-like chain. In contrast, the X-C lambda transcripts do not appear to encode a C lambda-related polypeptide in mature B cells. Thus, despite a 73% homology extending far beyond the exon sequences, the X and lambda 14.1 genes are expressed at different stages of B cell development and might serve different functions.

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Control of Expression of Immunoglobulin Genes

Cited by 13 publications

References 30 publications

Rearrangement and expression of endogenous immunoglobulin genes occur in many murine B cells expressing transgenic membrane IgM.

Rearrangement and expression of endogenous immunoglobulin genes occur in many murine B cells expressing transgenic membrane IgM.

Immunoglobulin lambda light-chain-related genes 14.1 and 16.1 are expressed in pre-B cells and may encode the human immunoglobulin omega light-chain protein.

Expression of a novel type of immunoglobulin C_λ transcripts in human mature B lymphocytes producing χ light chains

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Control of Expression of Immunoglobulin Genes

Cited by 13 publications

References 30 publications

Rearrangement and expression of endogenous immunoglobulin genes occur in many murine B cells expressing transgenic membrane IgM.

Rearrangement and expression of endogenous immunoglobulin genes occur in many murine B cells expressing transgenic membrane IgM.

Immunoglobulin lambda light-chain-related genes 14.1 and 16.1 are expressed in pre-B cells and may encode the human immunoglobulin omega light-chain protein.

Expression of a novel type of immunoglobulin Cλ transcripts in human mature B lymphocytes producing χ light chains

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Expression of a novel type of immunoglobulin C_λ transcripts in human mature B lymphocytes producing χ light chains