Incidence of novel N-glycosylation sites in the B-cell receptor of lymphomas associated with immunodeficiency

Forconi, F., Capello, D., Berra, E., Rossi, D., Gloghini, A., Cerri, M., Muti, G., Morra, E., Paulli, M., Magrini, U., Lucioni, M., Rambaldi, A., Lauria, F., Carbone, A., Stevenson, F.K. and Gaidano, G. (2004) Incidence of novel N-glycosylation sites in the B-cell receptor of lymphomas associated with immunodeficiency. British Journal of Haematology, 124 (5), 604-609. (doi:10.1111/j.1365-2141.2004.04816.x).

Abstract

Novel N-glycosylation sites are introduced by somatic mutation into the V genes of the majority of follicular lymphomas. Sites are positively selected and rare in normal memory B cells, indicating a potential role in tumour survival in the germinal centre (GC). The incidence of c. 40% in diffuse large B-cell lymphomas (DLBCL) parallels the known heterogenity of the disease. Immunodeficiency-related non-Hodgkin's lymphomas (NHL) include post-transplant lymphoproliferative disorders (PTLD) and acquired immunodeficiency syndrome-related NHL (AIDS-NHL). Most PTLD derive from B cells that carry mutated VH genes and that have completed the GC reaction. All AIDS-NHL carry mutated VH genes and variable features of GC or post-GC cells. To determine if N-glycosylation is a feature of immunodeficiency-related lymphomas, we analysed the VH genes of 19 PTLD and 36 AIDS-NHL. Novel sites were rare in PTLD (4/19), similar to memory B cells (P = 0·15). AIDS-NHL, including DLBCL and Burkitt's lymphomas (BL), showed heterogeneity with 16 of 36 (44%) having novel sites. The findings indicate no selection of N-glycosylation sites in PTLD, consistent with post-GC features. The variable incidence of N-glycosylation sites in AIDS-NHL mirrors that in DLBCL and sporadic BL of immunocompetent hosts, supporting the known heterogeneity of these disorders, and possibly pointing to distinct routes of tumour development.

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Contributors

Author: F. Forconi

Author: F.K. Stevenson

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