Chemokine receptor expression in B-cell lymphoproliferative disorders.

Chemokine receptors are expressed by many cells, including lymphoid cells, and function to mediate cell trafficking and localization. Normal B-cells have been reported to express CXCR3, CXCR4, CXCR5, CCR6 and CCR7, however changes in chemokine receptor expression during B-cell development and in B-cell lymphoproliferative disorders (BCLPDs) are incompletely understood, and could provide important information about normal B-cell development and about behavior of neoplastic B-cells. The objective was to perform a systematic study of chemokine receptor expression on B cells from normal subjects and from patients with a range of BCLPDs. Expression of the above chemokine receptors, and CCR5, were analyzed by flow cytometry on lymphocytes from normal controls (n=20), and samples of follicular centre cell lymphoma (FCCL, n=16), precursor B-acute lymphoblastic leukemia (Prec-B-ALL, n=16), chronic lymphocytic leukemia (CLL, n=21), small cell lymphocytic lymphoma (SLL, n=9), hairy cell leukemia (HCL, n=10) and other miscellaneous disorders (n=9). Normal B cells were typically positive for CXCR4, CXCR5 and CCR6, negative for CCR5 and variable for CCR7. Prec-B-ALL cells expressed CXCR4 but were negative for the other receptors. B-CLL cells lost expression of CCR6 but showed strong expression of CCR7. In contrast, SLL cells failed to express CCR7, but were otherwise similar to CLL cells. HCL cells showed absence of CXCR5 and CCR7, but interestingly all but one case expressed CCR5, whilst CD25-negative "variant" HCL cells did not express CCR5. FCCL cells down-regulated CXCR4 and CXCR5 expression and lost expression of CCR6 and CCR7. CXCR3 expression was highly variable on normal B-cells and on cells from BCLPDs, possibly due to its lability during processing. Distinct changes in chemokine receptor expression accompany B-cell development, whilst some BCLPDs show characteristic alterations that may be useful in phenotyping and in understanding biological behavior.