Abstract
ObjectiveThe declined immune response to infection causes significant higher morbidity and mortality in aging in spite of the coexisted hyperimmunoglobulinemia (HIG). This study is to reveal the cellular basis of HIG and mechanism of weakened HA-specific IgG response in aged mice and to test cell therapy in the treatment of age-related IgG antibody production deficiency with immunocyte adoptive transfer.MethodsBALB/c mice was immunized with Influenza A/Taiwan vaccine and challenged with the same strain of virus. ELISA was used to assess the levels of total immunoglobulins and antigen specific antibody response. The flow cytometry and ELISPOT were used to evaluate the frequencies of total immunoglobulin- and specific antibody-producing and secreting B lymphocytes. In vitro expanded mononuclear cells, CD4+ T lymphocytes and CD20+ B lymphocytes from old and young mice were adoptively transferred into influenza virus-challenged aged mice, and HA-specific IgG responses were observed.ResultsIt is found that old mice exhibited higher levels of total serum IgG, IgM and IgA, higher frequencies of IgG+, IgM+ and IgA+ cells, and greater antigen-specific IgM and IgA responses to influenza infection, in comparison to young mice. However, influenza antigen- specific IgG and its subclass responses in old mice were significantly lower.ConclusionThe retarded specific IgG response could be attributed to an insufficiency of immunoglobulin class switch in aging. Correlation analysis indicated that HIG and deficient specific IgG production in aged mice could be independent to each other in their pathogenesis. Correction of deficient specific IgG production by adoptive transfer of in vitro expanded and unexpanded CD4+ cells from immunized young mice suggests the CD4+ cell dysfunction contributes to the insufficiency of immunoglobulin class switch in aged mice. The transfusion of in vitro expanded lymphocytes could be a potential effective therapy for the age-related immunodeficiency and could play a role in the infection prevention in aging.
Highlights
Some hyperimmunoglobulinemia (HIG)-related diseases, such as Waldenstrom’s macroglobulinemia, angioimmunoblastic lymphadenopthy, multiple myeloma, amyloidosis and certain autoimmune diseases, occur in old people much more frequently than in the young [1,2,3,4]
The retarded specific IgG response could be attributed to an insufficiency of immunoglobulin class switch in aging
Correction of deficient specific IgG production by adoptive transfer of in vitro expanded and unexpanded CD4+ cells from immunized young mice suggests the CD4+ cell dysfunction contributes to the insufficiency of immunoglobulin class switch in aged mice
Summary
Some hyperimmunoglobulinemia (HIG)-related diseases, such as Waldenstrom’s macroglobulinemia, angioimmunoblastic lymphadenopthy, multiple myeloma, amyloidosis and certain autoimmune diseases, occur in old people much more frequently than in the young [1,2,3,4]. Such a high immunoglobulin (Ig) tendency does not seem to promote the immunity against infections in old people. To determine whether HIG in aging is accompanied by an alteration of antigen-specific antibody production, we examined influenza virus antigen-specific and –nonspecific IgG, IgM and IgA and assessed IgG+, IgM+ and IgA+ B cells with ELISA, ELISPOT assay and/or flow cytometry in old mice and young controls
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
