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International Immunology, Vol. 13, No. 4, 475-484, April 2001
© 2001 Japanese Society for Immunology

Predominance of a novel splenic B cell population in mice expressing a transgene that encodes multireactive antibodies: support for additional heterogeneity of the B cell compartment

Kathleen M. Tumas-Brundage1,, Evangelia Notidis1,, Lynn Heltemes1,, Xianghua Zhang, Lawrence J. Wysocki and Tim Manser1,

Department of Immunology, National Jewish Medical and Research Center and University of Colorado School of Medicine, Denver, CO 80262, USA
1 Kimmel Cancer Institute and the Department of Microbiology and Immunology, Jefferson Medical College, Philadelphia, PA 19107, USA

Correspondence to: T. Manser

We generated IgHµ{delta} transgenic mice using a VH gene that in A/J mice encodes multireactive BCR in the preimmune B cell compartment and is predominantly expressed by a memory B cell subpopulation. Most primary splenic B cells in these mice have a size, cell-surface phenotype and in vitro response profile distinct from mature follicular (B2), marginal zone (MZ) or B1 B cells, but are long-lived and appear to be slowly cycling. They reside in conventional B cell areas of the spleen and mount robust foreign antigen-driven germinal center responses, but do not efficiently differentiate to secretory phenotype. We propose that these qualities result from ongoing, low-avidity BCR–self-ligand interactions and promote entry into the memory pathway. Given these data, and the enormous diversity and characteristic multireactivity of the preimmune antibody repertoire, we also suggest that it may be more appropriate to view the primary B cell compartment as a continuum of functional and phenotypic `layers', rather than as a group of discrete B1, B2 and MZ subsets.

Keywords: B cell, development, memory, subsets, transgenic mice

The first two authors contributed equally to this work

Transmitting editor: J. Kearney


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