Key developmental transitions in human germinal center B cells are revealed by differential CD45RB expression.
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.
Jackson
Stephen M
SM
Molecular Immunogenetics Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Harp
Natessa
N
Patel
Darshna
D
Wulf
Jordan
J
Spaeth
Erich D
ED
Dike
Uzoamaka K
UK
James
Judith A
JA
Capra
J Donald
JD
D051997:ADP-ribosyl Cyclase 1 / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D015415:Biomarkers; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002469:Cell Separation; D005434:Flow Cytometry; D018858:Germinal Center / Q000166:cytology* / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007072:Immunoglobulin D / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D038041:Lymphopoiesis / Q000276:immunology*; D009154:Mutation / Q000235:genetics; D014066:Palatine Tonsil / Q000276:immunology; D020033:Protein Isoforms / Q000145:classification / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology
D015415:Biomarkers; D007072:Immunoglobulin D; D007135:Immunoglobulin Variable Region; D020033:Protein Isoforms; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D017493:Leukocyte Common Antigens; D051997:ADP-ribosyl Cyclase 1