Submitted March 19, 2008
Accepted August 20, 2008
Key developmental transitions in human germinal center B cells are revealed by differential CD45RB expression
Stephen M. Jackson, Natessa Harp, Darshna Patel, Jordan Wulf, Erich D. Spaeth, Uzoamaka K. Dike, Judith A. James, and J. Donald Capra*
Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States
Molecular Immunogenetics Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States
Department of Medicine and Pathology, University of Oklahoma Health Science Center, Oklahoma City, OK, United States
* Corresponding author; email: jdonald-capra{at}omrf.org.
We previously reported that RO+ expression correlated with increased mutation, activation, and selection among human germinal center (GC) B cells1;2. Here, we subdivided human tonsillar B cells, including IgD-CD38+ GC B cells into different fractions based on RB expression. Though each subset contained RB+ cells, when used as an intra-subset 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 GC B cells was followed by a dramatic increase during the GC-to-plasmablast (IgD-CD38++CD27+) and memory (IgD-CD38-CD27+) transition. Interestingly, RB+ GC B cells showed increased signs of terminal differentiation towards 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
