Expression of the BAFF-R (BR3) Is Positive in a Minority of Diffuse Large B Cell Lymphomas and Does Not Correlate with the Germinal Center or Non Germinal Center Origin of Lymphomatous Cells.

Abstract BAFF, a member of the TNF family, has been shown to be implicated in B cell maturation and survival through an interaction with its three receptors, BCMA, TACI and BAFF-R. Recent data revealed that it also plays a role in B cell malignancies. For exemple, an autocrine activation of the BAFF receptors could participate to oncogenesis during multiple myeloma or chronic lymphocytic leukemia. BAFF-R, the sole BAFF specific receptor, is expressed in a subset of Diffuse Large B Cell Lymphomas (DLBCL). Since BAFF-R activation in B cells leads to cell proliferation and survival, expression of this receptor in DLBCL could correlate with more aggressive lymphomas. DLBCL can be divided into prognostically important subgroups with germinal center B cell-like (GCB), activated B cell-like (ABC) and type 3 gene expression profiles using a cDNA microarray. The germinal center origin of malignant B cells in DLBCL can also be characterized by immunohistochemistry (IHC) according to CD10, Bcl6 CD138 and MUM1 expression. In this work, we investigated whether expression of BAFF-R in DLBCL correlate or not with the GCB vs non GCB phenotype of lymphomatous cells. Lymph nodes biopsies from 23 DLBCL (among whom 3 post-transplantation lymphomas and 1 AIDS-related DLBCL) were analyzed. In a first step, we characterized by IHC the precise phenotype of each DLBCL: CD10+/Bcl6+ DLBCL were classified into the germinal center (GCB) group (n=9), whereas CD10-/BCL6-/MUM1+ lymphomas defined the non germinal center (NGCB) one (n=14). Each DLBCL was then analyzed for BAFF-R expression by IHC. In agreement with a recent report, most of the DLBCL were found to be negative for BAFF-R expression (16 out of 23). Interestingly, 4 of the 9 GCB DLBCL were found to be BAFF-R positive (44%), whereas only 3 out of 14 (21%) in the NGCB group. Although the difference did not reach statistical significance, we concluded from this observation that a consequent percentage of GCB DLBCL express the specific receptor BAFF-R. Thus, we actually analyze the clinical and biological characteristics of BAFF-R positive DLBCL and investigate whether expression of BAFF-R could represent a bad prognosis factor in term of clinical outcome and response to treatment.