Stereotyped patterns of B-cell receptor in splenic marginal zone lymphoma.

Antigen stimulation may be important for splenic marginal zone lymphoma (SMZL) pathogenesis. To address this hypothesis, the occurrence of stereotyped B-cell receptors (BCR) was investigated in 133 SMZL (26 HCV+) compared with 4,414 HCDR3 sequences from public databases (PDB). Sixteen SMZL (12%) showed stereotyped BCR; 7/86 (8%) SMZL sequences retrieved from PDB also belonged to stereotyped HCDR3 subsets. Three categories of subsets were identified : 1) "SMZL-specific subsets" (n=5), composed only of 12 SMZL (9 HCV- from our series); 2) "Non-Hodgkin lymphoma-like subsets" (n=5), comprising 5 SMZL (4 from our series) clustering with other indolent lymphomas; 3) "CLL-like subsets" (n=6), comprising 6 SMZL (3 from our series) that belonged to known CLL subsets (n=4) or clustered with public CLL sequences. Immunoglobulin 3D modeling of 3 subsets revealed similarities in antigen binding regions not limited to HCDR3. Overall, data suggest that the pathogenesis of SMZL may involve also HCV-unrelated epitopes or an antigenic trigger common to other indolent lymphomas.