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 localisation. Normal B cells have been reported to express CXCR3, CXCR4, CXCRS, CCR6 and CCR7. However, changes in chemokine receptor expression during B-cell development and in B-cell lymphoproliferative disorders (BCLPDs) are incompletely understood, but could provide important information about normal B-cell development as well as behaviour of neoplastic B cells. The objective of this project 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, was analysed by flow cytometry on lymphocytes from normal controls (n=20), and samples of follicular centre cell lymphoma (FCCL, n=16), precursor B-acute lymphoblastic leukaemia (Prec—B-ALL, n=16), chronic lymphocytic leukaemia (CLL, n=21), small cell lymphocytic lymphoma (SLL, n=9), hairy cell leukaemia (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, the majority of 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 CDZS-negative ‘variant’ HCL cells did not express CCRS. FCCL cells downregulated 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 for phenotyping and understanding biological behaviour