CD93 is required for maintenance of antibody secretion and persistence of plasma cells in the bone marrow niche
- Stéphane Chevriera,1,
- Céline Gentona,1,
- Axel Kalliesb,
- Alexander Karnowskib,
- Luc A. Ottena,
- Bernard Malissenc,
- Marie Malissenc,
- Marina Bottod,
- Lynn M. Corcoranb,
- Stephen L. Nuttb and
- Hans Acha-Orbeaa,2
- aDepartment of Biochemistry, University of Lausanne, Chemin des Boveresses 155, 1066 Epalinges, Switzerland;
- bThe Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia;
- cCentre d'Immunologie de Marseille-Luminy, Institut National de la Santé et de la Recherche Médicale/Centre National de la Recherche Scientifique, Université de la Méditerranée, 13284 Marseille, France; and
- dMolecular Genetics and Rheumatology Section, Division of Medicine, Faculty of Medicine, Imperial College, Hammersmith Campus, London W12 0NN, United Kingdom
-
Edited by Gustav J. Nossal, University of Melbourne, Victoria, Australia, and approved January 16, 2009
-
↵1S.C. and C.G. contributed equally to this work. (received for review October 6, 2008)
Abstract
Plasma cells represent the end stage of B-cell development and play a key role in providing an efficient antibody response, but they are also involved in numerous pathologies. Here we show that CD93, a receptor expressed during early B-cell development, is reinduced during plasma-cell differentiation. High CD93/CD138 expression was restricted to antibody-secreting cells both in T-dependent and T-independent responses as naive, memory, and germinal-center B cells remained CD93-negative. CD93 was expressed on (pre)plasmablasts/plasma cells, including long-lived plasma cells that showed decreased cell cycle activity, high levels of isotype-switched Ig secretion, and modification of the transcriptional network. T-independent and T-dependent stimuli led to re-expression of CD93 via 2 pathways, either before or after CD138 or Blimp-1 expression. Strikingly, while humoral immune responses initially proceeded normally, CD93-deficient mice were unable to maintain antibody secretion and bone-marrow plasma-cell numbers, demonstrating that CD93 is important for the maintenance of plasma cells in bone marrow niches.
Footnotes
- 2To whom correspondence should be addressed. E-mail: hans.acha-orbea{at}unil.ch
-
Author contributions: S.C., L.A.O., and H.A.-O. designed research; S.C., C.G., A. Kallies, and A. Karnowski performed research; B.M., M.M., M.B., L.M.C., and S.L.N. contributed new reagents/analytic tools; S.C., C.G., A. Kallies, and A. Karnowski analyzed data; and S.C., A. Kallies, L.M.C., S.L.N., and H.A.-O. wrote the paper.
-
The authors declare no conflict of interest.
-
This article is a PNAS Direct Submission.
-
This article contains supporting information online at www.pnas.org/cgi/content/full/0809736106/DCSupplemental.
