Rapid polarization of Th2 cells during induction of antigen-specific IgE antibodies in vitro.
BACKGROUND
Type 2 T-helper cells (Th2) are involved in the regulation of the humoral immune response against antigens and allergens and directly affect which isotype will be produced. The mechanism that regulates antigen-specific IgE secretion and immune deviation is still not known.


OBJECTIVE
To delineate mechanisms behind antigen-specific IgE secretion we have used in vitro immunization and focused on T-cell phenotype and the activation status of the transcription factor NFkappaB.


METHODS
Peripheral blood lymphocytes (PBMC) from seronegative donors were immunized in vitro with a peptide consisting of both a T-cell and a B-cell epitope.


RESULTS
Antigen-specific IgE antibodies could be detected after a primary immunization, during which T-helper cells secreted type 2 cytokines. Specific IgE was also detected in the secondary immunization, but due to a rapid polarization from Th2 to Th1 phenotype, exogenous IL-4 was required for the specific IgE secretion. Analysis of NFkappaB activation in B and T cells during primary and secondary immunization showed that NFkappaB could be detected in both B and T cells during primary immunization, but was dependent on exogenous IL-4 in the secondary immunization.


CONCLUSIONS
This is the first evidence of antigen-specific IgE induction in vitro using naive B cells, demonstrating the involvement of T-helper cell phenotype and NFkappaB and demonstrates the usefulness of in vitro cultures to study the effect of antigens on human immunocytes.
Akesson
A
A
Department of Immunotechnology, Lund University, Sweden.
Ingvarsson
S
S
Brady
K
K
Moynagh
P
P
Borrebaeck
C A
CA
D000595:Amino Acid Sequence; D000941:Antigens / Q000737:chemistry / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D016764:Cell Polarity; D002478:Cells, Cultured; D000939:Epitopes; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D006801:Humans; D007114:Immunization; D007117:Immunization, Secondary; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000097:blood; D015847:Interleukin-4 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D013745:Tetanus Toxoid / Q000737:chemistry / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
D000941:Antigens; D000939:Epitopes; D015699:HIV Envelope Protein gp120; D016328:NF-kappa B; D010455:Peptides; D013745:Tetanus Toxoid; D015847:Interleukin-4; D007073:Immunoglobulin E