The Journal of Experimental Medicine
Cytokines Montreal 2008
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Published online 2 July 2001. doi:10.1084/jem.194.1.45
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© The Rockefeller University Press, 0022-1007/2001/7/45/ $5.00
The Journal of Experimental Medicine, Volume 194, Number 1, July 2, 2001 45-56

Original Article

A Coordinated Change in Chemokine Responsiveness Guides Plasma Cell Movements

Diana C. Hargreavesa, Paul L. Hymana, Theresa T. Lua, Vu N. Ngoa, Afshin Bidgola, Gen Suzukib, Yong-Rui Zouc, Dan R. Littmanc, and Jason G. Cystera
a Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, CA 94143
b Department of Clinical Studies, Radiation Effect Research Foundation, Hiroshima City 732-0815, Japan
c Howard Hughes Medical Institute, Skirball Institute of Biomolecular Medicine, New York University Medical Center, New York, NY 10016

Correspondence to: Jason G. Cyster, Dept. of Microbiology and Immunology, University of California at San Francisco, 513 Parnassus Ave., San Francisco, CA 94143-0414. Tel:415-502-6427 Fax:415-502-8424 E-mail:cyster{at}itsa.ucsf.edu.

Antibody-secreting plasma cells are nonrecirculatory and lodge in splenic red pulp, lymph node medullary cords, and bone marrow. The factors that regulate plasma cell localization are poorly defined. Here we demonstrate that, compared with their B cell precursors, plasma cells exhibit increased chemotactic sensitivity to the CXCR4 ligand CXCL12. At the same time, they downregulate CXCR5 and CCR7 and have reduced responsiveness to the B and T zone chemokines CXCL13, CCL19, and CCL21. We demonstrate that CXCL12 is expressed within splenic red pulp and lymph node medullary cords as well as in bone marrow. In chimeric mice reconstituted with CXCR4-deficient fetal liver cells, plasma cells are mislocalized in the spleen, found in elevated numbers in blood, and fail to accumulate normally in the bone marrow. Our findings indicate that as B cells differentiate into plasma cells they undergo a coordinated change in chemokine responsiveness that regulates their movements in secondary lymphoid organs and promotes lodgment within the bone marrow.

Key Words: CXCR4, CXCR5, CCR7, bone marrow, spleen


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