IL-4-dependent IgE switch in membrane IgA-positive human B cells.
IgE responses by human B cells, separated according to membrane Ig classes, were analyzed in a clonal assay using EL-4 thymoma cells as helper cells, T cell supernatant, and rIL-4. In cultures seeded by means of the autoclone apparatus of the FACS, IgE responses were generated frequently by either IgM (mu+/gamma-alpha-) or IgA (alpha +/mu-)-positive B cells (16 and 14% of the Ig producing wells, respectively), but rarely by IgG (gamma +/mu-)-positive B cells (1.3% of Ig producing wells). The total amounts of Ig secreted by IgM-, IgG-, or IgA-positive cells and the total proportions of responding autoclone wells (23-27%) were comparable. All IgE secretion was IL-4 dependent. When the Ig secretion patterns from alpha +/mu- vs alpha +/mu-epsilon- B cells were compared, most autoclone wells from both types of cells produced IgA only, and similar proportions of IgA producing wells (6.2 and 6.0%) also secreted IgE. In addition, IgE restricted responses occurred 6 times more frequently with alpha +/mu- than with alpha +/mu-epsilon- cells, which suggests that membrane IgA+E double-positive, IgE committed B cells occur in vivo. The isotype pattern generated by alpha +/mu-epsilon- B cells cannot be explained by a chance assortment of separate IgA and IgE precursors or by cytophilic antibody. Thus, IL-4 dependent switch to IgE occurred frequently in IgM- or IgA-positive, but rarely among total IgG-positive, B cells. This could be relevant to IgE production in mucosal tissues rich in IgA expressing B cells.
Department of Medicine, Geneva University Hospital, Switzerland.
X H
XH
Zhang
C
C
Werner-Favre
H Y
HY
Tang
N
N
Brouwers
J Y
JY
Bonnefoy
R H
RH
Zubler
D016175:B-Lymphocyte Subsets / Q000502:physiology*; D005812:Genes, Switch; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D007073:Immunoglobulin E / Q000378:metabolism*; D007132:Immunoglobulin Isotypes / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D007070:Immunoglobulin A; D007132:Immunoglobulin Isotypes; D007075:Immunoglobulin M; D015847:Interleukin-4; D007073:Immunoglobulin E