Natalizumab treatment leads to an increase in circulating CXCR3-expressing B cells

Abstract

<h4>OBJECTIVE: </h4><p>To study the effects of natalizumab treatment on subgroups of circulating peripheral blood B cell populations.</p><h4>METHODS: </h4><p>We studied the proportions and absolute numbers of CD19⁺CD20⁺, CD10⁺, and CD5⁺ B cell populations, and determined very late activation antigen-4 and chemokine receptor CXCR3, CCR5, and CCR6 expression on B cells in the peripheral blood of 14 natalizumab-treated patients with relapsing-remitting multiple sclerosis. Five blood samples per patient were obtained longitudinally before and during the first year of treatment. Blood samples were analyzed by 6-color flow cytometry.</p><h4>RESULTS: </h4><p>Proportions of B cells and CD10⁺ pre-B cells were significantly increased, and very late activation antigen-4 expression on the B cell surface was significantly decreased already after 1 week of natalizumab treatment. Natalizumab-induced sustained increase in the proportion and absolute number of CXCR3-expressing B cells was statistically significant after 1 month of treatment. There were no changes in the proportions of CCR5- or CCR6-expressing B cells.</p><h4>CONCLUSIONS: </h4><p>The rapid and persistent increase in circulating CXCR3-expressing B cells in response to natalizumab treatment possibly reflects the relevance of this chemokine receptor in controlling migration of B cells into the CNS in humans in vivo.<br /></p>