The Journal of Experimental Medicine
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Published 18 October 2004. doi:10.1084/jem.20040973
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 200, Number 8, 967-977
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Plasma Cell Ontogeny Defined by Quantitative Changes in Blimp-1 Expression

Axel Kallies, Jhagvaral Hasbold, David M. Tarlinton, Wendy Dietrich, Lynn M. Corcoran, Philip D. Hodgkin, and Stephen L. Nutt

The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 3050, Australia

Address correspondence to Stephen L. Nutt, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria, 3050, Australia. Phone: 61-3-9345-2483; Fax: 61-3-9347-0852; email: nutt{at}wehi.edu.au

Plasma cells comprise a population of terminally differentiated B cells that are dependent on the transcriptional regulator B lymphocyte–induced maturation protein 1 (Blimp-1) for their development. We have introduced a gfp reporter into the Blimp-1 locus and shown that heterozygous mice express the green fluorescent protein in all antibody-secreting cells (ASCs) in vivo and in vitro. In vitro, these cells display considerable heterogeneity in surface phenotype, immunoglobulin secretion rate, and Blimp-1 expression levels. Importantly, analysis of in vivo ASCs induced by immunization reveals a developmental pathway in which increasing levels of Blimp-1 expression define developmental stages of plasma cell differentiation that have many phenotypic and molecular correlates. Thus, maturation from transient plasmablast to long-lived ASCs in bone marrow is predicated on quantitative increases in Blimp-1 expression.

Key Words: Prdm1 • B-lymphopoiesis • plasma cell • antibody secretion • terminal differentiation • syndecan-1

Abbreviations used in this paper: ASC, antibody-secreting cell; Blimp-1, B lymphocyte–induced maturation protein 1; BrdU, bromodeoxyuridine; ES, embryonic stem; IRES, internal ribosome entry site; KLH, keyhole limpet hemocyanin; NP, 4(hydoxy-3)-nitrophenyl acetyl; Synd-1, syndecan-1.


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