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

Abstract

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.

Cryoglobulin/albumin complexes in a patient with severe autoimmune syndrome

“…The fact that all relative autoantibody titres exceeded normal values to the degree of hypergammaglobulinaemia suggests their clustered up-regulation. Hence, up-regulation of anti-albumin antibodies in our patient differs from that observed in patients with chronic hepatitis B, where antibodies to monomeric albumin are selectively up-regulated (11).…”

Immunoglobulin (Ig)G purified from human sera mirrors intravenous Ig human leucocyte antigen (HLA) reactivity and recognizes one's own HLA types, but may be masked by Fab complementarity-determining region peptide in the native sera

“…Supporting this contention, it was shown that the levels of anti‐albumin IgG autoantibodies were higher than normal in both acute and chronic hepatitis patients, but that those levels decreased to normal when the patients recovered . It was also shown that the circulatory pool of B cells from the majority of chronic hepatitis B surface antigen carriers contained sensitized B cells that, when stimulated, secreted IgG antibodies with specificity for human serum albumin .…”