Immunoglobulin VH gene expression among extranodal marginal zone B-cell lymphomas of the ocular adnexa

PURPOSE. Most lymphomas of the ocular adnexa are primary extranodal non-Hodgkin's lymphomas of the B-cell type, with the most common lymphoma subtype being the extranodal marginal-zone B-cell lymphoma (EMZL). Analysis of somatic mutations iii the variable (V) region of the Ig heavy (H)-chain gene segment suggests that EMZL development in other locations is dependent on antigen stimulation. The purpose of this study was to analyze the presence of somatic hypermutations in clonally rearranged Ig H-chain V genes of this lymphoma entity in the ocular adnexa and to estimate whether the mutation pattern is compatible with antigen selection. METHODS. Twenty-six cases of EMZL of the ocular adnexa were diagnosed on the basis of morphology, histology, and immunohistology. A nested polymerase chain reaction (PCR) was performed on DNA extracted from paraffin sections. The isolated PCR products were sequenced and compared with published V, germline segments to determine the number of somatic mutations in the complementarity-determining region (CDR) 2 and framework (FW) region 3. RESULTS. The number of somatic mutations in the cases of EMZL varied between 0 and 24: Five cases involved 0 to 3 somatic mutations, and the remaining 21 cases involved 4 to 24 mutations. Based on the ratio of replacement (R) to silent (S) mutations in the CDR2 or FW3 regions, antigen selection seems to have occurred in 60% of ocular adnexal FMZL. The V(H)3 family was the most commonly expressed germline V-H family (54%), followed by V(H)4 (23%), with biased usage of the latter. Some germline V-H genes used included DP-8, DP-10, DP-53, DP-63 (V(H)4.21), and DP-49, which are frequently used by autoantibodies (e.g., rheumatoid factors) and natural autoantibodies. CONCLUSIONS. EMZLs of the ocular adnexa have an Ig H-chain mutation pattern that supports the concept that they represent a clonal expansion of post-germinal-center memory B-cells in most instances. In two thirds of cases, antigen selection may have occurred, and autoantibodies may have a role in their development.