The Journal of Immunology, Vol 150, Issue 2 543-549, Copyright © 1993 by American Association of Immunologists

ARTICLES

Repertoire diversity of antibody response to bacterial antigens in aged mice. III. Phosphorylcholine antibody from young and aged mice differ in structure and protective activity against infection with Streptococcus pneumoniae

C Nicoletti, X Yang and J Cerny
Department of Microbiology and Immunology, School of Medicine, University of Maryland, Baltimore 21201.

Aging in mice is accompanied by qualitative changes in the antibody repertoire to phosphorylcholine (PC), a natural epitope of certain pneumococci. The PC-specific mAb from young/adult (2-4 mo) BALB/c mice are uniformly encoded by the canonical IgV genes of T15 family, whereas the antibody from aged mice (> or = 20 mo) are molecularly heterogeneous, being encoded by various VH and VL genes of non-T15 families. Interestingly the young/adult and aged BALB/c mice produce comparable amounts of antibodies to PC regardless of the molecular shift in the antibody repertoire. This finding prompted our study on the relative ability of PC antibodies from young and aged donors to protect mice against virulent infection with type 3 pneumococci. Passive administration (i.p.) of pooled, PC-specific mAb generated from young donors (all from the T15 Ig gene family) protected the recipients against subsequent i.p. challenge with a lethal dose of Streptococcus pneumoniae strain WU2, in a dose-dependent manner. In contrast, a mixture of PC mAb from aged donors (all from non-T15 families) failed to protect the mice against the infection, even at the highest amount of administered (100 micrograms of mAb/recipient). Average affinity of the aged mAb for the free hapten (PC-chloride) as well as their binding to the bacteria was lower than that of the young mAb. Similarly, affinity-purified serum PC antibody from S. pneumoniae vaccine- immunized young mice afforded a measurable degree of passive protection against the pneumococcal infection whereas a similar dose of serum PC antibody from aged mice did not. Further experiments showed that PC mAb from young donors were equally protective in either young or aged recipients challenged with the bacteria. These results demonstrate that the aged immune system may, in some instances, produce high levels of antibody that are structurally different and less protective against microbial infection.

This article has been cited by other articles:

				D. Frasca, A. M. Landin, R. L. Riley, and B. B. Blomberg Mechanisms for Decreased Function of B Cells in Aged Mice and Humans J. Immunol., March 1, 2008; 180(5): 2741 - 2746. [Abstract] [Full Text] [PDF]

				B. Garcia, E. Neninger, A. de la Torre, I. Leonard, R. Martinez, C. Viada, G. Gonzalez, Z. Mazorra, A. Lage, and T. Crombet Effective Inhibition of the Epidermal Growth Factor/Epidermal Growth Factor Receptor Binding by Anti-Epidermal Growth Factor Antibodies Is Related to Better Survival in Advanced Non-Small-Cell Lung Cancer Patients Treated with the Epidermal Growth Factor Cancer Vaccine Clin. Cancer Res., February 1, 2008; 14(3): 840 - 846. [Abstract] [Full Text] [PDF]

				G. L. Goldberg, O. Alpdogan, S. J. Muriglan, M. V. Hammett, M. K. Milton, J. M. Eng, V. M. Hubbard, A. Kochman, L. M. Willis, A. S. Greenberg, et al. Enhanced Immune Reconstitution by Sex Steroid Ablation following Allogeneic Hemopoietic Stem Cell Transplantation J. Immunol., June 1, 2007; 178(11): 7473 - 7484. [Abstract] [Full Text] [PDF]

				K. Kolibab, S. L. Smithson, B. Rabquer, S. Khuder, and M. A. J. Westerink Immune Response to Pneumococcal Polysaccharides 4 and 14 in Elderly and Young Adults: Analysis of the Variable Heavy Chain Repertoire Infect. Immun., November 1, 2005; 73(11): 7465 - 7476. [Abstract] [Full Text] [PDF]

				S. L. Smithson, K. Kolibab, A. K. Shriner, N. Srivastava, S. Khuder, and M. A. J. Westerink Immune Response to Pneumococcal Polysaccharides 4 and 14 in Elderly and Young Adults: Analysis of the Variable Light Chain Repertoire Infect. Immun., November 1, 2005; 73(11): 7477 - 7484. [Abstract] [Full Text] [PDF]

				S. M. Eaton, E. M. Burns, K. Kusser, T. D. Randall, and L. Haynes Age-related Defects in CD4 T Cell Cognate Helper Function Lead to Reductions in Humoral Responses J. Exp. Med., December 20, 2004; 200(12): 1613 - 1622. [Abstract] [Full Text] [PDF]

				D. Frasca, E. Van der Put, R. L. Riley, and B. B. Blomberg Reduced Ig Class Switch in Aged Mice Correlates with Decreased E47 and Activation-Induced Cytidine Deaminase J. Immunol., February 15, 2004; 172(4): 2155 - 2162. [Abstract] [Full Text] [PDF]

				L. Haynes, S. M. Eaton, E. M. Burns, T. D. Randall, and S. L. Swain CD4 T cell memory derived from young naive cells functions well into old age, but memory generated from aged naive cells functions poorly PNAS, December 9, 2003; 100(25): 15053 - 15058. [Abstract] [Full Text] [PDF]

				S. L. Harris, W. J. King, W. Ferris, and D. M. Granoff Age-Related Disparity in Functional Activities of Human Group C Serum Anticapsular Antibodies Elicited by Meningococcal Polysaccharide Vaccine Infect. Immun., January 1, 2003; 71(1): 275 - 286. [Abstract] [Full Text] [PDF]

				M. Sanchez, K. Lindroth, E. Sverremark, A. G. Fernandez, and C. Fernandez The response in old mice: positive and negative immune memory after priming in early age Int. Immunol., October 1, 2001; 13(10): 1213 - 1221. [Abstract] [Full Text] [PDF]

				Y. Sun, Y.-i. Hwang, and M. H. Nahm Avidity, Potency, and Cross-Reactivity of Monoclonal Antibodies to Pneumococcal Capsular Polysaccharide Serotype 6B Infect. Immun., January 1, 2001; 69(1): 336 - 344. [Abstract] [Full Text] [PDF]

				S. L. Harris, M. K. Park, M. H. Nahm, and B. Diamond Peptide Mimic of Phosphorylcholine, a Dominant Epitope Found on Streptococcus pneumoniae Infect. Immun., October 1, 2000; 68(10): 5778 - 5784. [Abstract] [Full Text] [PDF]

				A. H. Lucas and D. C. Reason Aging and the Immune Response to the Haemophilus influenzae Type b Capsular Polysaccharide: Retention of the Dominant Idiotype and Antibody Function in the Elderly Infect. Immun., April 1, 1998; 66(4): 1752 - 1754. [Abstract] [Full Text] [PDF]

				Q.-S. Mi, L. Zhou, D. H. Schulze, R. T. Fischer, A. Lustig, L. J. Rezanka, D. M. Donovan, D. L. Longo, and J. J. Kenny Highly reduced protection against Streptococcus pneumoniae after deletion of a single heavy chain gene in mouse PNAS, May 23, 2000; 97(11): 6031 - 6036. [Abstract] [Full Text] [PDF]