Human immune response to group A streptococcal carbohydrate (A-CHO). I. Quantitative and qualitative analysis of the A-CHO-specific B cell population responding in vitro to polyclonal and specific activation.
The immune response to the group-specific carbohydrate of group A streptococci (A-CHO) provides an informative in vitro model for the investigation of several aspects of human anticarbohydrate immune responses. A-CHO-specific B cells can be polyclonally activated by pokeweed mitogen (PWM), and, specifically, by in vitro immunization with streptococcal vaccine. High levels of A-CHO-specific antibodies, mainly directed to the immunodominant side chain N-acetyl-D-glucosamine (GlcNAc), occur in healthy adult individuals. Serum antibody levels are reflected in high frequencies of precursor B cells among peripheral blood lymphocytes. In one particular case, greater than 15% of all B cells activated by PWM for IgM production were found to produce IgM anti-A-CHO antibodies, as determined in limiting dilution experiments, as well as by analyzing Ig concentrations in bulk culture experiments. The case with the lowest proportion observed had 0.3% A-CHO-specific B cells among IgM-producing B cells. Preferential PWM activation of anti-A-CHO-producing B cells could be excluded. The comparison of the proportions of anti-A-CHO IgM produced in vivo, and of B cells producing antibodies of this specificity in peripheral blood, suggests a similar distribution of specific precursor B cells in the antibody-producing lymphoid tissue compartments and in peripheral blood. However, nearly all specific antibodies produced in vitro belong to the IgM isotype, whereas IgG anti-A-CHO in high amounts, mostly exceeding the specific IgM, was found only among anti-A-CHO antibodies produced in vivo. Low anti-A-CHO IgG production was seen in polyclonally activated as well as in antigen-activated cultures, whereas, in contrast, total IgG was produced in considerable amounts after polyclonal activation. This suggests a different distribution pattern, and/or diverse differentiation requirements for anti-A-CHO-producing B cells, compared with other B cell species.
Emmrich
F
F
Schilling
B
B
Eichmann
K
K
D000328:Adult; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000942:Antigens, Bacterial / Q000276:immunology*; D001402:B-Lymphocytes / Q000145:classification* / Q000378:metabolism; D001426:Bacterial Proteins; D001666:Binding Sites, Antibody; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D008934:Mitogens / Q000494:pharmacology; D011135:Polysaccharides, Bacterial / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D013234:Stem Cells / Q000378:metabolism; D013291:Streptococcus / Q000276:immunology
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D000939:Epitopes; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008934:Mitogens; D011135:Polysaccharides, Bacterial; C034866:streptococcal group A mitogen; C036112:streptococcal polysaccharide group A