Mechanistic insights into the impairment of memory B cells and antibody production in the elderly

被引:30
作者
Aberle, Judith H. [1 ]
Stiasny, Karin [1 ]
Kundi, Michael [2 ]
Heinz, Franz X. [1 ]
机构
[1] Med Univ Vienna, Dept Virol, Vienna, Austria
[2] Med Univ Vienna, Ctr Publ Hlth, Vienna, Austria
关键词
Immunosenescence; B memory cells; Aging; TBE vaccination; CD4(+)T cells; CD154; TERMINAL DIFFERENTIATION; HUMORAL IMMUNITY; AGE; ENCEPHALITIS; LYMPHOCYTES; VACCINATION; MICE; ACTIVATION; INFECTION; RESPONSES;
D O I
10.1007/s11357-011-9371-9
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
It is well established that immunologic memory generated early in life can be maintained into old age and mediate robust anamnestic antibody responses. Little is known, however, about the initiation of memory B cells in the elderly. We have conducted a prospective analysis of the quantities and functionalities of antigen-specific B cell responses and its association with the functional helper CD4(+)T cell responses. The ability of na < ve B cells from old (60-80 years) and young (20-31 years) humans to establish functional memory was examined following primary and booster vaccination with an inactivated-virus vaccine against tick-borne encephalitis. Our data show that the number of antigen-specific memory B cells generated during primary vaccination was similar to 3-fold lower in old than in young individuals. The maintenance and booster responsiveness of these memory B cells were not compromised, as evidenced by similar increases in specific memory B cell frequencies upon revaccination in old and young adults. In contrast, the Ab response mediated per memory B cell after revaccination was dramatically diminished in the elderly. Also, antigen-specific IL-2-positive CD4(+)T cell responses were strongly reduced in the elderly and displayed an excellent correlation with Ab titres. The data suggest that the dramatically lower antibody response in the elderly could only partially be accounted for by the reduced B cell numbers and was strongly correlated with profound functional defects in CD4 help.
引用
收藏
页码:371 / 381
页数:11
相关论文
共 50 条
[11]   Aging down-regulates the transcription factor E2A, activation-induced cytidine deaminase, and Ig class switch in human B cells [J].
Frasca, Daniela ;
Landin, Marie ;
Lechner, Suzanne C. ;
Ryan, John G. ;
Schwartz, Robert ;
Riley, Richard L. ;
Blomberg, Bonnie B. .
JOURNAL OF IMMUNOLOGY, 2008, 180 (08) :5283-5290
[12]   Aging Affects Human B Cell Responses [J].
Frasca, Daniela ;
Blomberg, Bonnie B. .
JOURNAL OF CLINICAL IMMUNOLOGY, 2011, 31 (03) :430-435
[13]   Immune Complex-Mediated Enhancement of Secondary Antibody Responses [J].
Goins, Chelsey L. ;
Chappell, Craig P. ;
Shashidharamurthy, Rangaiah ;
Selvaraj, Periasamy ;
Jacob, Joshy .
JOURNAL OF IMMUNOLOGY, 2010, 184 (11) :6293-6298
[14]   The continuing spread of West Nile virus in the Western Hemisphere [J].
Gubler, Duane J. .
CLINICAL INFECTIOUS DISEASES, 2007, 45 (08) :1039-1046
[15]   Tick-borne encephalitis -: pathogenesis, clinical course and long-term follow-up [J].
Haglund, M ;
Günther, G .
VACCINE, 2003, 21 :S11-S18
[16]   Insufficient protection for healthy elderly adults by tetanus and TBE vaccines [J].
Hainz, U ;
Jenewein, B ;
Asch, E ;
Pfeiffer, KP ;
Berger, P ;
Grubeck-Loebenstein, B .
VACCINE, 2005, 23 (25) :3232-3235
[17]  
Halstead S B., 2008, VACCINES, P311
[18]   The effect of age on the cognate function of CD4+ T cells [J].
Haynes, L ;
Eaton, SM .
IMMUNOLOGICAL REVIEWS, 2005, 205 :220-228
[19]   CD4 T cell memory derived from young naive cells functions well into old age, but memory generated from aged naive cells functions poorly [J].
Haynes, L ;
Eaton, SM ;
Burns, EM ;
Randall, TD ;
Swain, SL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (25) :15053-15058
[20]  
Holzmann H, 1996, J MED VIROL, V48, P102, DOI 10.1002/(SICI)1096-9071(199601)48:1<102::AID-JMV16>3.0.CO