MUTATION ANALYSIS OF THE REARRANGED IMMUNOGLOBULIN HEAVY-CHAIN GENES OF MARGINAL ZONE CELL LYMPHOMAS INDICATES AN ORIGIN FROM DIFFERENT MARGINAL ZONE B-LYMPHOCYTE SUBSETS

Marginal zone cell lymphoma is a recently described entity among the n on-Hodgkin's lymphomas. It likely originates from the marginal zone B cells in the spleen and equivalent cells in the lymph node and extrano dal tissues. Recent evidence indicates that marginal zone B cells are functionally heterogeneous and may differ with respect to the pattern of somatic hypermutation in their Ig variable genes. io test whether m arginal zone lymphomas may originate from different subsets of margina l zone B cells, we performed a sequence and mutation analysis of the r earranged Ig heavy chain (IgH) variable genes (V-H) of a series of 14 cases of marginal zone lymphoma, occurring in the spleen (4), the lymp h node (4), the stomach (2), the orbit (2), the tongue (1), and the sk in (1). Our data show that marginal zone cell lymphomas preferentially rearrange the V(H)4, V(H)3, and V(H)1 family genes, without preferenc e for any particular V-H gene. Somatic mutations are present in 13 cas es; one case of marginal zone cell lymphoma of the skin showed a germl ine configuration of the rearranged V-H gene. Mutation analysis shows evidence of antigen selection in three cases of marginal zone cell lym phoma, one of the spleen, stomach, and orbit, respectively. No evidenc e of antigen selection was present in the other cases, These data indi cate that marginal zone cell lymphomas may arise from different subset s of marginal zone B cells. In addition, lymphomagenesis may not be tr iggered by antigen in all cases of marginal zone cell lymphoma. (C) 19 98 by The American Society of Hematology.