Early lymphocyte activation in elderly humans: impaired T and T-dependent B cell responses.
Immunosenescence is characterized by an increase in autoantibody production. Because both T and B cell stimulation are key events for producing antibodies, we investigated early T and B cell activation by means of CD23 and CD40L (two very early activation antigens). PBMC from elderly humans (EH) were studied following culture with either medium, anti-CD3mAb, rIL-4, or PMA + ionomycin. CD23 expression on elderly B cells after anti-CD3 challenge of PBMC, a reflect of T-dependent B cell activation, was clearly defective. Conversely, CD23 expression on EH B cells following activation with soluble factors as rIL-4 was preserved. CD40L expression was also impaired in EH T cells following anti-CD3 challenge. However, activation by means of PMA and/or ionomycin was preserved both in T cells (CD40L expression) and in B cells (CD23 expression). These results indicate that a defective T-dependent B cell activation related to defective T cell activation located between surface membrane and PKC/ionomycin function is an intrinsic characteristic of immunosenescence. We have not found intrinsic B-cell defects, and we conclude that the characteristically impaired early B cell activation in EH is mostly due to T cell defects.
Fernández-Gutiérrez
B
B
Service of Rheumatology, Hospital Clínico San Carlos, Madrid, Spain. chernandez@pulso.com
Jover
J A
JA
De Miguel
S
S
Hernández-García
C
C
Vidán
M T
MT
Ribera
J M
JM
Bañares
A
A
Serra
J A
JA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D017252:CD3 Complex / Q000378:metabolism; D023201:CD40 Ligand; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D017455:Receptors, IgE / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D008562:Membrane Glycoproteins; D017455:Receptors, IgE; D023201:CD40 Ligand; D015847:Interleukin-4; D013755:Tetradecanoylphorbol Acetate