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Silent Development of Memory Progenitor B Cells¹

Katja Aviszus^*, Xianghua Zhang and Lawrence J. Wysocki^2,*

^* Integrated Department of Immunology, National Jewish Medical and Research Center and University of Colorado School of Medicine, Denver, CO 80206; and Isogenis, Denver, CO 80206

T cell-dependent immune responses generate long-lived plasma cells and memory B cells, both of which express hypermutated Ab genes. The relationship between these cell types is not entirely understood. Both appear to emanate from the germinal center reaction, but it is unclear whether memory cells evolve while obligatorily generating plasma cells by siblings under all circumstances. In the experiments we report, plasma cell development was functionally segregated from memory cell development by a series of closely spaced injections of Ag delivered during the period of germinal center development. The injection series elevated serum Ab of low affinity, supporting the idea that a strong Ag signal drives plasma cell development. At the same time, the injection series produced a distinct population of affinity/specificity matured memory B cells that were functionally silent, as manifested by an absence of corresponding serum Ab. These cells could be driven by a final booster injection to develop into Ab-forming cells. This recall response required that a rest period precede the final booster injection, but a pause of only 4 days was sufficient. Our results support a model of memory B cell development in which extensive affinity/specificity maturation can take place within a B cell clone under some circumstances in which a concomitant generation of Ab-forming cells by siblings does not take place.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants AI033613 and AI048108.

² Address correspondence and reprint requests to Dr. Lawrence J. Wysocki, Department of Immunology, K902a, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206. E-mail address: wysockiL{at}njc.org

³ Abbreviations used in this paper: AFC, Ab-forming cell; GC, germinal center; Ars, p-azophenylarsonate; Tg, transgenic; Sulf, sulfanilic acid; RT, room temperature; SA, streptavidin; ABTS, 2'2'-azino-bis(3-ethylbenz-thiazoline-6-sulfonic acid); Eu, europium; KLH, keyhole limpet hemocyanin; PNA, peanut lectin agglutinin; I₅₀, inhibited by 50%.