IgG subclass switch capacity is low in switched and in IgM-only,   but high in IgD+IgM+, post-germinal center (CD27+) human B   cells.
Recent studies have shown that in humans the germinal center reactions produce three types of V(D)J mutated B cells in similar proportions, i.e. Ig-switched, IgD-IgM+ (IgM-only) and IgD+IgM+ cells, and that together they form the CD27+ compartment of recirculating B cells. We investigated the Ig isotype switch capacity of these cells. Peripheral blood B subsets were sorted and IgG subclass secretion in presence or absence of IL-4 was compared in B cell assays which lead to Ig secretion in all (coculture with EL-4 thymoma cells) or only in CD27+ (CD40L stimulation) B cells. Already switched IgG+ B cells showed no significant sequential switch and IgM-only cells also had a low switch capacity, but IgD+CD27+ switched as much as IgD+CD27- B cells to all IgG subclasses. Thus, in switched B cells some alterations compromising further switch options occur frequently; IgM-only cells may result from aborted switch. However, IgD+CD27+ human B cells, extensively V(D)J mutated and "naive" regarding switch, build up a repertoire of B cells combining (1) novel cross-reactive specificities, (2) increased differentiation capacity (including after T-independent stimulation by Staphylococcus aureus Cowan I) and (3) the capacity to produce appropriate isotypes when they respond to novel pathogens.
Division of Hematology, Department of Medicine, Geneva University Hospital, Geneva, Switzerland.
C
C
Werner-Favre
F
F
Bovia
P
P
Schneider
N
N
Holler
M
M
Barnet
V
V
Kindler
J
J
Tschopp
R H
RH
Zubler
D016175:B-Lymphocyte Subsets / Q000378:metabolism*; D018858:Germinal Center / Q000378:metabolism*; D006801:Humans; D017578:Immunoglobulin Class Switching; D007072:Immunoglobulin D / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000145:classification*; D007075:Immunoglobulin M / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis*
D007072:Immunoglobulin D; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7