In vitro enhancement of immunoglobulin gene expression in chronic lymphocytic leukemia

J. Cossman, L. M. Neckers, Rita Braziel, J. B. Trepel, S. J. Korsmeyer, A. Bakhshi

Research output: Contribution to journalArticle

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Abstract

B cell chronic lymphocytic leukemia (CLL) cells appear to be arrested in their differentiation so that little immunoglobulin is secreted in most cases. To determine their capacity for further differentiation we stimulated cells from a series of 10 cases of CLL with a phorbol ester and assayed for production of immunoglobulin protein, accumulation of immunoglobulin mRNA, and alterations in cell surface markers. We found that cells from all cases were induced to secrete monoclonal immunoglobulin of the same heavy and light chain type as the surface membrane immunoglobulin type. Immunoglobulin secretion was preceded by a rapid increase in the levels of mRNA coding for IgM, predominantly the secretory form, μ(s)-mRNA, rather than the membrane form, μ(m)-mRNA. A similar selection of μ(s)- over μ(m)-mRNA is known to occur in plasma cells by a mechanism of differential processing of mRNA from a single μ-chain gene. Except for a decline in the expression of surface IgD, cell surface determinants remained unaffected both in terms of the percentage of positive cells and the relative number of sites per cell. In contrast to previous studies, these results indicate that CLL cells consistently retain the capacity to further differentiate toward plasma cells and secrete immunoglobulin. The immunoglobulin secretion is mediated, at least in part, by a developmentally regulated increment in μ(s)-mRNA.

Original languageEnglish (US)
Pages (from-to)587-592
Number of pages6
JournalJournal of Clinical Investigation
Volume73
Issue number2
StatePublished - 1984
Externally publishedYes

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Immunoglobulin Genes
B-Cell Chronic Lymphocytic Leukemia
Immunoglobulins
Gene Expression
Messenger RNA
Plasma Cells
Immunoglobulin Light Chains
Immunoglobulin D
Immunoglobulin Heavy Chains
B-Cell Antigen Receptors
Membranes
Phorbol Esters
In Vitro Techniques
Cell Differentiation
Cell Count
Genes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Cossman, J., Neckers, L. M., Braziel, R., Trepel, J. B., Korsmeyer, S. J., & Bakhshi, A. (1984). In vitro enhancement of immunoglobulin gene expression in chronic lymphocytic leukemia. Journal of Clinical Investigation, 73(2), 587-592.

In vitro enhancement of immunoglobulin gene expression in chronic lymphocytic leukemia. / Cossman, J.; Neckers, L. M.; Braziel, Rita; Trepel, J. B.; Korsmeyer, S. J.; Bakhshi, A.

In: Journal of Clinical Investigation, Vol. 73, No. 2, 1984, p. 587-592.

Research output: Contribution to journalArticle

Cossman, J, Neckers, LM, Braziel, R, Trepel, JB, Korsmeyer, SJ & Bakhshi, A 1984, 'In vitro enhancement of immunoglobulin gene expression in chronic lymphocytic leukemia', Journal of Clinical Investigation, vol. 73, no. 2, pp. 587-592.
Cossman, J. ; Neckers, L. M. ; Braziel, Rita ; Trepel, J. B. ; Korsmeyer, S. J. ; Bakhshi, A. / In vitro enhancement of immunoglobulin gene expression in chronic lymphocytic leukemia. In: Journal of Clinical Investigation. 1984 ; Vol. 73, No. 2. pp. 587-592.
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