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

• Published in: Blood 2009-04, Vol.113 (17), p.3999-4007
• Main Authors: Jackson, Stephen M., Harp, Natessa, Patel, Darshna, Wulf, Jordan, Spaeth, Erich D., Dike, Uzoamaka K., James, Judith A., Capra, J. Donald
• Format: Article
• Language: English
• Subjects: ADP-ribosyl Cyclase 1 - immunology; B-Lymphocytes - immunology; Biological and medical sciences; Biomarkers; Cell Membrane - immunology; Cell Membrane - metabolism; Cell Separation; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Germinal Center - cytology; Germinal Center - immunology; Hematologic and hematopoietic diseases; Humans; Immunity, Innate - immunology; Immunobiology; Immunoglobulin D - immunology; Immunoglobulin Variable Region - immunology; Immunologic Memory - immunology; Leukocyte Common Antigens - classification; Leukocyte Common Antigens - genetics; Leukocyte Common Antigens - immunology; Leukocyte Common Antigens - metabolism; Lymphocyte Activation - immunology; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; Lymphopoiesis - immunology; Medical sciences; Mutation - genetics; Palatine Tonsil - immunology; Protein Isoforms - classification; Protein Isoforms - immunology; Protein Isoforms - metabolism; Time Factors; Tumor Necrosis Factor Receptor Superfamily, Member 7 - immunology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2008-03-145979

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 IgD−CD38+ 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 (IgD−CD38++CD27+) and memory (IgD−CD38−CD27+) 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.