Identification of a Human Follicular Dendritic Cell Molecule That Stimulates Germinal Center B Cell Growth

doi:10.1084/jem.191.6.1077

Published online 20 March 2000.

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© The Rockefeller University Press, 0022-1007/2000/3/1077/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 6, March 20, 2000 1077-1084

Brief Definitive Report

Identification of a Human Follicular Dendritic Cell Molecule That Stimulates Germinal Center B Cell Growth

Li Li^a, Xin Zhang^a, Sharlotte Kovacic^b, Andrew J. Long^b, Karen Bourque^b, Clive R. Wood^b, and Yong Sung Choi^a
^a Laboratory of Cellular Immunology, Alton Ochsner Medical Foundation, New Orleans, Louisiana 70121
^b Genetics Institute, Inc., Cambridge, Massachusetts 02140

Correspondence to: Yong Sung Choi, Laboratory of Cellular Immunology, Alton Ochsner Medical Foundation, 1516 Jefferson Hwy., New Orleans, LA 70121. Tel:504-842-3035 Fax:504-842-3381 E-mail:ychoi{at}ochsner.org.

Released online: 20 March 2000

The initial interaction between B cells and follicular dendriticcells (FDCs) appears to be essential for germinal center (GC)formation. To identify molecules regulating this interaction,we generated FDC-staining monoclonal antibodies (mAbs) and screenedthem for their ability to block FDC-mediated costimulation ofgrowth and differentiation of CD40-stimulated B cells. Usingone of the inhibitory mAbs, 8D6, we expression cloned the cDNAencoding the 8D6 antigen (Ag) from a human FDC line, HK. The8D6 Ag is a novel protein of 282 amino acids that is expressedabundantly on FDCs. Monolayers of COS cells transiently transfectedwith the 8D6 Ag cDNA stimulate B cell growth. The mAb 8D6 blocksthe costimulatory function completely. The inhibitory activityof the mAb 8D6 was demonstrated to be due to an inhibition ofcell cycle progression of CD40 ligand–stimulated GC Bcells. In addition, the mAb 8D6 inhibits the growth of a lymphomaof GC origin, L3055, which depends on FDCs or HK cells for itsgrowth. These findings suggest that the primary function ofFDCs in the GC is to stimulate B cell growth. An FDC signalmolecule, 8D6 Ag, may be an important molecule to mediate thisfunction.

Key Words: follicular dendritic cell molecule, B cell proliferation, germinalcenter

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