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Blood, 23 April 2009, Vol. 113, No. 17, pp. 3999-4007.
Prepublished online as a Blood First Edition Paper on December 4, 2008; DOI 10.1182/blood-2008-03-145979.


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IMMUNOBIOLOGY

Key developmental transitions in human germinal center B cells are revealed by differential CD45RB expression

Stephen M. Jackson1,2, Natessa Harp1, Darshna Patel1, Jordan Wulf1, Erich D. Spaeth1, Uzoamaka K. Dike1, Judith A. James2,3, and J. Donald Capra1

1 Molecular Immunogenetics Research Program and 2 Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City; and 3 Department of Medicine and Pathology, University of Oklahoma Health Science Center, Oklahoma City

We previously reported that RO+ expression correlated with increased mutation, activation, and selection among human germinal center (GC) B cells. Here, we subdivided human tonsillar B cells, including IgDCD38+ GC B cells, into different fractions based on RB expression. Although each subset contained RB+ cells, when used as an intrasubset marker, differential RB expression effectively discriminated between phenotypically distinct cells. For example, RB+ GC B cells were enriched for activated cells with lower AID expression. RB inversely correlated with mutation frequency, demonstrating a key difference between RB- and RO-expressing GC B cells. Reduced RB expression during the transition from pre-GC (IgM+IgD+CD38+CD27) to GCB cells was followed by a dramatic increase during the GC-to-plasmablast (IgDCD38++CD27+) and memory (IgDCD38CD27+) transition. Interestingly, RB+ GC B cells showed increased signs of terminal differentiation toward CD27+ post-GC early plasmablast (increased CD38 and RO) or early memory (decreased CD38 and RO) B cells. We propose that as in T cells, differential RB expression directly correlates with development- and function-based transitions in tonsillar B cells. Application of this RB:RO system should advance our understanding of normal B-cell development and facilitate the isolation of more discrete B-cell populations with potentially different propensities in disease pathogenesis.


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