Immunoglobulin synthesis by normal and neoplastic human B-Lymphocytes

Gordon, John (1978) Immunoglobulin synthesis by normal and neoplastic human B-Lymphocytes. University of Southampton, Doctoral Thesis.

Abstract

Cell populations from forty-six cases of B-cell neoplasia were investigated for their capacity to synthesize immunoglobulin (Ig) in vitro. Tumour cells from cases of chronic lymphocytic leukaemia, leukaemic reticuloendotheliosia and small non-cleaved non-follicular centre cell lymphoma were characterized by surface Ig expression and morphological features usually associated with immature B-lymphocytes and exhibited patterns of Ig synthesis consistent with such cell types. These "immature" B-cell neoplasms synthesized light chain (LC) in molar excess of heavy chain (11C) and in a majority of cases free LC was the only detectable supernatant Ig product. Follicular centre cell lymphomas, considered to be neoplasms of more mature B-lymphocyte types, showed high rates of Ig synthesis and secretion and synthesized HC andLC in approximate molar balance. These findings are discussed in relation to normal B-lymphocyte maturation.Other B-cell models were investigated including cell lines which had been derived from the tissue of patients with a variety of haematological malignancies. Although the cells in the culture could not be related to the original disorder, the findings suggested that established lines had considerable potential as models for studying Ig synthesis. Lymphocytes from patients with primary immunodeficiency were also investigated and consistent with the neoplastic model, were found to secrete free LC as their major Ig product. Excess LC production was also demonstrated with normal spleen and lymph node populations. The significance of free LC secretion by normal and neoplastic B-cells is discussed.

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