Restoration of Retarded Influenza Virus-specific Immunoglobulin Class Switch in Aged Mice.
OBJECTIVE
The 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.


METHODS
BALB/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 vitroexpanded 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.


RESULTS
It 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.


CONCLUSIONS
The 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 ofin vitroexpanded 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 ofin vitroexpanded lymphocytes could be a potential effective therapy for the age-related immunodeficiency and could play a role in the infection prevention in aging.
ZYX Biotech Company, 1452 Halsey Way, Suite 100, Carrollton, TX 75007, USA; Influenza Research Center, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Yongxin
Y
Zhang
ZYX Biotech Company, 1452 Halsey Way, Suite 100, Carrollton, TX 75007, USA; Influenza Research Center, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Ying
Y
Wang
ZYX Biotech Company, 1452 Halsey Way, Suite 100, Carrollton, TX 75007, USA.
Monica
M
Zhang
Influenza Research Center, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Lin
L
Liu
Influenza Research Center, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Innocent N
IN
Mbawuike