Regulation of the immune response to hepatitis B virus and human serum albumin. III. Induction of anti-albumin antibody secretion in vitro by C-gene-derived proteins in peripheral B cells from chronic carriers of HBsAg.
The circulatory pool of B cells from the majority (11/13) of chronic hepatitis B surface antigen (HBsAg) carriers contained sensitized B cells with the capacity to secrete IgG antibodies with specificity for human serum albumin (HSA), when stimulated with E. coli-derived core protein at low concentrations in vitro. The IgG anti-HSA secretion was dependent upon and regulated by T cells, and optimal secretion was obtained at T/B-cell ratios of 1.0-4.0, varying for different individuals. The level of anti-HSA secretion was higher for patients with on-going viral replication as assessed by hepatitis B virus (HBV)-DNA in serum. Culture supernatants containing anti-HSA antibodies also contained anti-HBc antibodies, as detected by enzyme-linked immunosorbent assay (ELISA) where the solid phase was charged with E. coli-derived core protein, or the synthetic peptides corresponding to the 75-84 and 132-147 sequences in the C region of HBV. In contrast, IgG anti-HBc (E. coli-derived), but no anti-HSA or anti-HBc 75-84, 132-147 antibodies, were detected at similar T/B-cell ratios in cell cultures from 5/6 individuals with naturally acquired immunity to hepatitis B. These data indicate that peripheral B cells from the majority of HB-immune donors are sensitized to unique (e.g. non-albumin associated) structures in the nucleocapsid of HBV, while B cells in the majority of chronic HBsAg carriers are sensitized to linear C-gene-derived structures in association with the host 'self'-component HSA.
Hellström
U B
UB
Department of Infectious Diseases, Karolinska Institute, Roslagstull Hospital, Stockholm, Sweden.
Sylvan
S P
SP
D000328:Adult; D000368:Aged; D000418:Albumins / Q000276:immunology; D000917:Antibody Formation; D005260:Female; D006508:Hepatitis Antibodies; D006509:Hepatitis B / Q000276:immunology; D006512:Hepatitis B Core Antigens / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology*; D006801:Humans; D007109:Immunity; D007156:Immunologic Memory; D008297:Male; D008875:Middle Aged; D012709:Serum Albumin / Q000276:immunology*; D014758:Viral Core Proteins / Q000276:immunology
D000418:Albumins; D006508:Hepatitis Antibodies; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D012709:Serum Albumin; D014758:Viral Core Proteins