The repertoire diversity and magnitude of antibody responses to bacterial antigens in aged mice: I. Age-associated changes in antibody responses differ according to the mouse strain

Nicoletti, Claudio; Černý, Jan

doi:10.1016/0008-8749(91)90180-j

Cited by 42 publications

(20 citation statements)

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“…The latter diminution of function may be secondary to age related defects in T cells. However, given the intrinsic changes in B lymphoid progenitors described above, it would not be surprising if cell autonomous changes in B cells from old mice underlie, at least in part, decreased isotype switching (Nicoletti and Cerny, 1991), reduced expression of costimulatory molecules (Zheng et al, 1997), and defects in B cell receptor signaling (Whisler and Grants, 1993).…”

Section: The Age-related Decline In B Lymphopoiesis Results In a Redumentioning

confidence: 99%

Aging, B lymphopoiesis, and patterns of leukemogenesis

Signer

Montecino‐Rodriguez

Dorshkind

2007

Experimental Gerontology

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The production of B lymphocytes begins to decline steadily early in adult life and is severely compromised in the elderly. This occurrence has been attributed to intrinsic defects in early hematopoietic progenitors and B cell precursors as well as to microenvironmental changes in aged bone marrow. The aim of this review is to present an overview of B lymphocyte senescence and its underlying causes, and to discuss its impact on immune function and leukemogenesis in aged individuals.

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Section: The Age-related Decline In B Lymphopoiesis Results In a Redumentioning

confidence: 99%

Aging, B lymphopoiesis, and patterns of leukemogenesis

Signer

Montecino‐Rodriguez

Dorshkind

2007

Experimental Gerontology

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“…For example, aged mice have decreased frequencies of B cells responsive to some antigens, such as the haptens 2,4-dinitrophenyl (DNP) [20] and (4-hydroxy-3-nitrophenyl)acetyl (NP) [21]. In contrast, the frequencies of B cells for other antigens are either unchanged, or, in some cases, increased with age [22][23][24]. More detailed analyses of clonal composition have led to the notion that while some specificities are maintained within the aged B cell repertoire, the relative representation of particular IgVH gene families shifts, and the responsive repertoire is relatively reduced in overall clonotypic diversity.…”

Section: Aging Alters Humoral Immune Responsesmentioning

confidence: 97%

“…About 90% of all IMM B cells are lost to these so-called central tolerance mechanisms. Once the surviving IMM B cells exit the BM, they continue to undergo selection based on BCR specificity during the TR stages Cell-intrinsic Myeloid skewing of HSC [83] Reduced E47, E2A in pro-B and pre-B cells [84,105,106] Reduced IL-7R levels [40] Shifts in Vh repertoire [30,107] Repertoire shifts [22,[25][26][27]97] Increased autoreactivity Reduced E47, AID [84,105,108,109] Micro-environmental Reduced HSC niche capacity [31,85] Reduced IL-7 production [86] Architectural changes [110]; possible link to homing of PCs…”

Section: Aging Impacts B Lymphocyte Generation Selection and Homeosmentioning

confidence: 99%

New Cells in Old Mice: The ABCs of Humoral Immunosenescence

Hao¹,

Oropallo²,

Scholz³

et al. 2012

TOLSJ

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Dampened humoral immune responses and increased propensity for autoimmune and inflammatory diseases are hallmarks of aging. Here, we summarize recent progress in understanding how aging affects humoral immunity, focusing on the discovery of a phenotypically and functionally unique B cell subset in aged mice, its potential role in immunosenescence, and its relationship to increased inflammation and autoimmunity.Keywords: Age, B cell homeostasis, function. OVERVIEWAging is a complex process characterized by functional declines in multiple physiologic systems. Age-related alterations in the immune system, a spectrum of changes that are in toto termed "immunosenescence," yield enhanced susceptibility to infectious diseases, increased propensity for inflammatory responses and autoantibody production, and consequently, increased morbidity and mortality [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. Understanding the mechanisms through which age-associated phenomena yield the overall immunosenescent phenotype presents a fundamental and challenging biological problem. Multiple factors contribute to this general deterioration of immune activity, encompassing both cell-intrinsic changes and alterations in lymphoid organ microenvironments. In particular, determining how age-associated changes result in modified homeostatic relationships among steady-state lymphocyte pools, and how this in turn impacts the initiation and quality of adaptive immune responses, may provide the keys to effective prophylaxis and intervention. In this review, we briefly summarize global shifts in humoral immune responsiveness that emerge with age, followed by a detailed consideration of changes in the genesis and homeostasis of B lymphocyte populations. Finally, we focus on a recently described B lineage subset that emerges with age [15,16], and discuss how the shifting palette of functional B cell subsets may contribute to the global landscape of immunosenescence. AGING ALTERS HUMORAL IMMUNE RESPONSESProtective humoral immunity requires maintaining both naïve and antigen-experienced B cell subsets that respond robustly to pathogens, yet maintain self-tolerance. Multiple studies have revealed that, in contrast to healthy young adults, aged individuals display blunted humoral responses to both new and previously encountered antigens, as well as increases in autoantibody levels [4,7,11,13,[17][18][19]. Accordingly, studies over the last several decades have interrogated the basis for this array of features. Table I summarizes some of the changes in B cell development, dynamics and function that have been revealed by these efforts.Early work focused primarily upon whether the frequency or clonal composition of responsive B cells changes in aged individuals, as well as whether hallmarks of effective humoral immune responses are altered. Examinations of how aging influences responding B cell frequencies, using model antigens in mice, have yielded mixed results. For example, aged mice have decreased frequencies of B cells responsive to some...

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“…The PC-specific response in BALB/c and D1.LP mice differed in regard to either its magnitude and idiotypic repertoire. 11,12 Almost all PC-antibody produced by BALB/c mice were T15 + while only a minority of those produced by D1.LP were T15 + . In addition, it was reported that BALB/c mice have detectable levels of T15 + immunoglobulin in normal preimmune sera, presumably due to an environmental stimulation.…”

Section: Discussionmentioning

confidence: 99%

“…It was demonstrated that the PCresponse differed according to the mouse strain in regard to its magnitude and Id repertoire. 11 For example, BALB/c mice were able to mount a vigorous response to PC while D1.LP was one of the poorest responder strains to Pn administration and in this mouse strain the response was characterized by a much lower proportion of T15 + antibody. 12 We decided to address the question as to whether a different level of circulating T15 idiotype may regulate the anti-T15 antibody response and we speculated that the high level of T15 in BALB/c mice may be able to render these mice tolerant to the T15 Id itself.…”

Section: Introductionmentioning

confidence: 99%

Autologous anti‐idiotypic antibody response is regulated by the level of circulating complementary idiotype

Borghesi

Nicoletti

1996

Immunology

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SUMMARYBALB/c mice injected with lyophilized vaccine from Streptococcus pneumoniae R36a (Pn) predominantly responded with antibody molecules the vast majority of which expressed the public idiotype T15 and were directed to the immunodominant epitope phosphorylcholine (PC). However, after a single immunization with Pn vaccine young (3-month-old) BALB/c mice did not produce any specific anti-T15 antibody response. In contrast, young D1.LP mice were able to mount a specific anti-T15 response upon primary immunization with pneumococcal vaccine. The anti-PC response in the two mouse strains differed in that the proportion of antibody molecules that expressed the T15 idiotype for Pn-primed D1.LP mice showed a smaller proportion of PC-specific antibody expressing the T15 idiotype. Neonatal injection of anti-T15 monoclonal antibodies led to a long-term suppression of the PC-specific T15 B-cell clones but at young/adult age these mice maintained the ability to produce a normal amount of PC-specific antibody. Interestingly, the idiotypically-suppressed BALB/c mice mounted a significant anti-T15 response during the primary response to Pn. We interpreted these data as showing that the level of circulating idiotype may regulate the production of the complementary antiidiotypic antibody. In addition, in vitro experiments demonstrated that the lack of the anti-T15 response during primary antibody response in BALB/c mice is probably because of a state of tolerance that is regulated by T cells.

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The repertoire diversity and magnitude of antibody responses to bacterial antigens in aged mice: I. Age-associated changes in antibody responses differ according to the mouse strain

Cited by 42 publications

References 28 publications

Aging, B lymphopoiesis, and patterns of leukemogenesis

Aging, B lymphopoiesis, and patterns of leukemogenesis

New Cells in Old Mice: The ABCs of Humoral Immunosenescence

Autologous anti‐idiotypic antibody response is regulated by the level of circulating complementary idiotype

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