The Journal of Experimental Medicine
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Published online 18 June 2001.
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© The Rockefeller University Press, 0022-1007/2001/6/1393/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 12, June 18, 2001 1393-1402

Original Article

Aberrant High Expression of B Lymphocyte Chemokine (Blc/Cxcl13) by C11b+Cd11c+ Dendritic Cells in Murine Lupus and Preferential Chemotaxis of B1 Cells towards Blc

Sho Ishikawaa, Taku Satoa, Masaaki Abeb, Shigenori Nagaia, Nobuyuki Onaia, Hiroyuki Yoneyamac, Yan-yun Zhanga, Takuji Suzukia, Shin-ichi Hashimotoa, Toshikazu Shiraib, Martin Lippd, and Kouji Matsushimaa

a Department of Molecular Preventive Medicine, School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan
b Department of Pathology, Juntendo University School of Medicine, Tokyo 113-8421, Japan
c Department of Internal Medicine, Niigata University School of Medicine, Niigata 951-8122, Japan
d Max-Delbruck Center for Molecular Medicine, Berlin 13092, Germany
Department of Molecular Preventive Medicine, School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.81-3-5684-229781-3-5841-3431

koujim{at}m.u-tokyo.ac.jp

We observed here that the expression of B lymphocyte chemokine (BLC/CXCL13) was markedly enhanced in the thymus and kidney in aged (NZB x NZW)F1 (BWF1) mice developing lupus nephritis, but not in similarly aged NZB and NZW mice. BLC-positive cells were present in the cellular infiltrates in the target organs with a reticular pattern of staining. CD11b+CD11c+ dendritic cells were increased in the thymus and spleen in aged BWF1 mice and identified as the major cell source for BLC. CD4+ T cells as well as B cells were dramatically increased in the thymus in aged BWF1 mice, whereas no increase was observed in aged NZB and NZW mice. B1/B2 ratio in the thymus was significantly higher than those in the spleen and peripheral blood in aged BWF1 mice. Interestingly, BLC showed preferential chemotactic activity for B1 cells derived from several mouse strains, including nonautoimmune mice. Cell surface CXCR5 expression on B1 cells was significantly higher than that on B2 cells. Thus, aberrant high expression of BLC by myeloid dendritic cells in the target organs in aged BWF1 mice may play a pivotal role in breaking immune tolerance in the thymus and in recruiting autoantibody-producing B cells in the development of murine lupus.

Key Words: chemokine • lupus • dendritic cells • B1 cells • T cells

Abbreviations used in this paper: APC, allophycocyanin; BLC, B lymphocyte chemokine; DC, dendritic cell; FCM, flow cytometer; FDC, follicular DC; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; HRP, horseradish peroxidase; RT, reverse transcription.

© 2001 The Rockefeller University Press


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