The Journal of Experimental Medicine
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Published online 14 February 2005. doi:10.1084/jem.20042060
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© The Rockefeller University Press, 0022-1007
The Journal of Experimental Medicine


Article

Early appearance of germinal center–derived memory B cells and plasma cells in blood after primary immunization

Elizabeth J. Blink, Amanda Light, Axel Kallies, Stephen L. Nutt, Philip D. Hodgkin, and David M. Tarlinton

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

CORRESPONDENCE David M. Tarlinton: tarlinton{at}wehi.edu.au

Immunization with a T cell–dependent antigen elicits production of specific memory B cells and antibody-secreting cells (ASCs). The kinetic and developmental relationships between these populations and the phenotypic forms they and their precursors may take remain unclear. Therefore, we examined the early stages of a primary immune response, focusing on the appearance of antigen-specific B cells in blood. Within 1 wk, antigen-specific B cells appear in the blood with either a memory phenotype or as immunoglobulin (Ig)G1 ASCs expressing blimp-1. The memory cells have mutated VH genes; respond to the chemokine CXCL13 but not CXCL12, suggesting recirculation to secondary lymphoid organs; uniformly express B220; show limited differentiation potential unless stimulated by antigen; and develop independently of blimp-1 expression. The antigen-specific IgG1 ASCs in blood show affinity maturation paralleling that of bone marrow ASCs, raising the possibility that this compartment is established directly by blood-borne ASCs. We find no evidence for a blimp-1–expressing preplasma memory compartment, suggesting germinal center output is restricted to ASCs and B220+ memory B cells, and this is sufficient to account for the process of affinity maturation.


Abbreviations used: ASC, antibody-secreting cell; GC, germinal center; HSA, human serum albumin; NP, (4-hydroxy-3- nitrophenyl)acetyl; V, variable.

E.J. Blink's present address is Sanquin Research at the Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, 1066 CX, Amsterdam, Netherlands.


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