Somatic mutation analysis of IgH variable regions reveals that tumor cellsof most parafollicular (monocytoid) B-cell lymphoma, splenic marginal zoneB-cell lymphoma, and some hairy cell leukemia are composed of memory B lymphocytes

The cell of origin of parafollicular (monocytoid) B cell lymphoma (PBCL), s plenic marginal zone lymphoma (SMZL), and hairy cell leukemia (HCL) is cont roversial. To better understand the relationship between these low-grade B- cell neoplasms, we analyzed the nucleotide sequences of the rearranged immu noglobulin heavy (IgH) chain variable (V) region of the clonal population o f cells in five cases of PBCL, four cases of SMZL, and seven cases of HCL t o determine whether these neoplasms could be differentiated by the degree o f somatic mutation in the IgH V gene or by the IgH V gene family usage. DNA was extracted from diagnostic material and clonality confirmed by PCR. The DNA was reamplified using V heavy chain family specific primers, and the a mplicons were sequenced. Sequences were compared with germline IgH V gene s equences, and base changes were determined to be silent or to represent ami no acid replacements by using three different methods. Four of five (80%) c ases of PBCL, three of four (75%) cases of SMZL, and three of seven (43%) c ases of HCL showed evidence of antigen selection, suggesting that these neo plasms involved clonal expansions of postgerminal center memory lymphocytes . Only SMZL showed a preferential usage of V(H)1 family genes. HUM PATHOL 3 0:306-312. Copyright (C) 1999 by W.B. Saunders Company.