Molecular analysis reveals somatically mutated and unmutated clonal and oligoclonal B cells in T-cell-rich B-cell lymphoma

Abstract

This paper describes the immunohistology and molecular genetics of 18 cases of T-cell-rich B-cell lymphoma (TCRBL). In all cases, the large B cells stained strongly for CD20, with more variable expression of CD79a, and were negative for CD30 and CD15. The majority of T cells were predominantly positive for TIA-1 and negative for CD57; a large population of histiocytes was present in all cases. Epstein-Barr virus (EBV)-coded RNA (EBER) was found in B blasts from four cases and in one case was present among the background lymphoid cells. IgH PCR products were generated in 16/18 cases and revealed clonal, oligoclonal and polyclonal PCR products in 12, two and two cases, respectively. In addition, TCRG clonal gene rearrangements were identified in two cases. TCRB gene rearrangements were polyclonal. Sequence analysis of seven cases with clonal/oligoclonal IgH gene rearrangements revealed functional sequences with predominant V(H)3 gene usage associated with various D genes and J(H)4 or J(H)6 gene segments. Four cases displayed varying degrees of replacement and silent mutations (1.8-21%), with one case exhibiting intraclonal heterogeneity; the distribution of mutations was indicative of antigen selection in three cases. The remaining three cases, including two cases with functional oligoclonal IgH rearrangements, harboured unmutated V region genes. The EBV-positive cases were associated with clonal, oligoclonal and polyclonal PCR products and with mutated and germline clonal sequences. These data indicate that TCRBL may be a heterogeneous entity associated with clonal and oligoclonal B cells derived from both germinal centre and naïve B cells.