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Natural killer cell‐dependent immunoglobulin G2a anti‐bovine serum albumin (BSA) response elicited by high molecular weight dextran–BSA conjugates associated with dextran‐mediated macrophage–natural killer cell interaction
Author(s) -
Ediriwickrema C. P.,
Tonkonogy S. L.,
Hammerberg B.
Publication year - 2000
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2000.00135.x
Subject(s) - bovine serum albumin , splenocyte , dextran , antibody , serum albumin , microbiology and biotechnology , chemistry , biology , immunology , biochemistry
Summary The roles of the interferon‐γ (IFN‐γ) and interleukin‐12 (IL‐12) produced during natural killer (NK) cell interaction with macrophages (Mφ) were investigated as the basis for the induction of immunoglobulin G2a (IgG2a) anti‐bovine serum albumin (BSA) responses by high molecular weight dextran conjugated to BSA (HMW‐DEX–BSA). BALB/c mice immunized with HMW‐DEX–BSA produced significantly higher levels of both IgG1 and IgG2a anti‐BSA than did mice immunized with BSA alone. Both IgG1 and IgG2a anti‐BSA levels were higher in mice immunized with BSA conjugated to dextran of molecular weight (MW) 5 000 000–40 000 000 compared with dextran of MW 10 000–60 000. The enhancement of anti‐BSA IgG2a levels but not of anti‐BSA IgG1 levels was inhibited when free BSA was added to the HMW‐DEX–BSA conjugate. NK cell depletion during HMW‐DEX–BSA immunization of mice resulted in significantly lower anti‐BSA IgG2a levels without affecting anti‐BSA IgG1 levels. Naive splenocytes or Mφ + NK cell co‐cultures incubated with HMW‐DEX or HMW‐DEX–BSA produced higher IFN‐γ levels than splenocytes or co‐cultures incubated with BSA alone. HMW‐DEX stimulated both IFN‐γ and IL‐12 production by Mφ + NK cell co‐cultures in a dose‐dependent manner. DEX‐induced IFN‐γ production by NK cells was dependent upon the presence of IL‐12, and IL‐12 production by Mφ was dependent upon the presence of IFN‐γ in these co‐cultures. Both Mφ and NK cells bound DEX to their surfaces. These data demonstrate that BSA linked to HMW‐DEX enhanced both T‐helper‐1‐ and T‐helper‐2‐associated antibody responses to BSA. The results also indicate an IL‐12‐dependent positive feedback interaction between NK cells and Mφ that supports a NK cell/IFN‐γ‐dependent mechanism for enhancement of anti‐BSA IgG2a antibody responses in mice immunized with HMW‐DEX–BSA protein conjugates.