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.
Werner-Favre
C
C
Division of Hematology, Department of Medicine, Geneva University Hospital, Geneva, Switzerland.
Bovia
F
F
Schneider
P
P
Holler
N
N
Barnet
M
M
Kindler
V
V
Tschopp
J
J
Zubler
R H
RH
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