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Age-Associated B Cells: A T-bet–Dependent Effector with Roles in Protective and Pathogenic Immunity
Open accessAbstract
A newly discovered B cell subset, age-associated B cells, expresses the transcription factor T-bet, has a unique surface phenotype, and accumulates progressively with age. Moreover, B cells with these general features are associated with viral infections and autoimmunity in both mice and humans. In this article, we review current understanding of the characteristics, origins, and functions of these cells. We also suggest that the protective versus pathogenic actions of these cells reflect appropriate versus aberrant engagement of regulatory mechanisms that control the Ab responses to nucleic acid–containing Ags.
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“Age-associated B cells (ABCs; CD11c+T-bet+) and regulatory T cells (Tregs) are key regulators of immune tolerance in aging, and their expansion or loss, respectively, has been implicated in age-related autoimmunity and chronic inflammation [25–29].”
From PLCγ2 deficiency compromises systemic immune tolerance and erodes myelin homeostasis while enhancing oxidative metabolism in the mouse brain (2026) · cites this paper as [25]
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Cites
Chronic Inflammation (Inflammaging) and Its Potential Contribution to Age-Associated Diseases
Franceschi, C., & Campisi, J. (2014) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glu057 · Cited by 3,891
Molecular Signature of CD8+ T Cell Exhaustion during Chronic Viral Infection
Wherry, E. J., Ha, S.-J., Kaech, S. M., Haining, W. N., Sarkar, S., Kalia, V., Subramaniam, S., Blattman, J. N., Barber, D. L., & Ahmed, R. (2007) · Immunity · doi:10.1016/j.immuni.2007.09.006 · Cited by 2,103
X-inactivation profile reveals extensive variability in X-linked gene expression in females
Carrel, L., & Willard, H. F. (2005) · Nature · doi:10.1038/nature03479 · Cited by 2,097
Chromatin–IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors
Leadbetter, E. A., Rifkin, I. R., Hohlbaum, A. M., Beaudette-Zlatanova, B. C., Shlomchik, M. J., & Marshak‐Rothstein, A. (2002) · Nature · doi:10.1038/416603a · Cited by 1,929
Molecular Signature of CD8+ T Cell Exhaustion during Chronic Viral Infection
Wherry, E. J., Ha, S., Kaech, S. M., Haining, W. N., Sarkar, S., Kalia, V., Subramaniam, S., Blattman, J. N., Barber, D. L., & Ahmed, R. (2007) · Immunity · doi:10.1016/j.immuni.2007.11.006 · Cited by 1,355
The aging immune system: primer and prospectus
Miller, R. A. (1996) · Science · doi:10.1126/science.273.5271.70 · Cited by 1,165
Christensen, S. R., Shupe, J., Nickerson, K., Kashgarian, M., Flavell, R. A., & Shlomchik, M. J. (2006) · Immunity · doi:10.1016/j.immuni.2006.07.013 · Cited by 1,090
Moir, S. L., Ho, J., Malaspina, A., Wang, W., DiPoto, A. C., O’Shea, M. A., Roby, G. A., Kottilil, S., Arthos, J. A., Proschan, M. A., et al. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20072683 · Cited by 894
Rubtsov, A. V., Rubtsova, K., Fischer, A., Meehan, R. T., Gillis, J. Z., Kappler, J. W., & Marrack, P. (2011) · Blood · doi:10.1182/blood-2011-01-331462 · Cited by 808
Self-citationFcγRIV: A Novel FcR with Distinct IgG Subclass Specificity
Nimmerjahn, F., Bruhns, P., Horiuchi, K., & Ravetch, J. V. (2005) · Immunity · doi:10.1016/j.immuni.2005.05.010 · Cited by 672
A B-cell subset uniquely responsive to innate stimuli accumulates in aged mice
Hao, Y., O'Neill, P., Naradikian, M. S., Scholz, J. L., & Cancro, M. P. (2011) · Blood · doi:10.1182/blood-2011-01-330530 · Cited by 622
Self-citationAllman, D., & Pillai, S. (2008) · Current Opinion in Immunology · doi:10.1016/j.coi.2008.03.014 · Cited by 536
T-bet regulates IgG class switching and pathogenic autoantibody production
Peng, S. L., Szabo, S. J., & Glimcher, L. H. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.082114899 · Cited by 498
Complement receptor 2/CD21− human naive B cells contain mostly autoreactive unresponsive clones
Isnardi, I., Ng, Y.-S., Menard, L. C., Meyers, G., Saadoun, D., Srdanovic, I., Samuels, J., Berman, J., Buckner, J. H., Cunningham‐Rundles, C., et al. (2010) · Blood · doi:10.1182/blood-2009-09-243071 · Cited by 483
Jacob, C. O., van der Meide, P. H., & McDevitt, H. O. (1987) · The Journal of Experimental Medicine · doi:10.1084/jem.166.3.798 · Cited by 391
Centenarians as a model for healthy aging
Franceschi, C., & Bonafè, M. (2003) · Biochemical Society Transactions · doi:10.1042/bst0310457 · Cited by 384
Serum interferon levels in patients with systemic lupus erythematosus
Ytterberg, S. R., & Schnitzer, T. J. (1982) · Arthritis & Rheumatism · doi:10.1002/art.1780250407 · Cited by 382
Interferon-gamma is required for lupus-like disease and lymphoaccumulation in MRL-lpr mice.
Balomenos, D., Rumold, R., & Theofilopoulos, A. N. (1998) · Journal of Clinical Investigation · doi:10.1172/jci750 · Cited by 348
Ehlers, M., Fukuyama, H., McGaha, T. L., Aderem, A. A., & Ravetch, J. V. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20052438 · Cited by 338
Rakhmanov, M., Keller, B., Gutenberger, S., Foerster, C., Hoenig, M., Driessen, G. J. A., van der Burg, M., van Dongen, J. J. M., Wiech, E., Visentini, M., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0901984106 · Cited by 334
A new CD21low B cell population in the peripheral blood of patients with SLE
Wehr, C., Eibel, H., Masilamani, M., Illges, H., Schlesier, M., Peter, H., & Warnatz, K. (2004) · Clinical Immunology · doi:10.1016/j.clim.2004.05.010 · Cited by 308
Rubtsova, K., Rubtsov, A. V., van Dyk, L. F., Kappler, J. W., & Marrack, P. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1312348110 · Cited by 300
Self-citationThe Decline in B Lymphopoiesis in Aged Mice Reflects Loss of Very Early B-Lineage Precursors
Miller, J. P., & Allman, D. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.5.2326 · Cited by 255
Kipps, T. J., Parham, P., Punt, J. A., & Herzenberg, L. A. (1985) · The Journal of Experimental Medicine · doi:10.1084/jem.161.1.1 · Cited by 248
CD11c-Expressing B Cells Are Located at the T Cell/B Cell Border in Spleen and Are Potent APCs
Rubtsov, A. V., Rubtsova, K., Kappler, J. W., Jacobelli, J., Friedman, R. S., & Marrack, P. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1500055 · Cited by 245
Self-citationWarnatz, K. (2002) · Immunobiology · doi:10.1078/0171-2985-00198 · Cited by 215
Discriminating gene expression profiles of memory B cell subpopulations
Ehrhardt, G. R. A., Hijikata, A., Kitamura, H., Ohara, O., Wang, J. O., & Cooper, M. D. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20072682 · Cited by 198
In senescence, age‐associated B cells secrete TNF α and inhibit survival of B‐cell precursors*
Ratliff, M., Alter, S., Frasca, D., Blomberg, B. B., & Riley, R. L. (2013) · Aging Cell · doi:10.1111/acel.12055 · Cited by 183
Divergent transcriptional programming of class-specific B cell memory by T-bet and RORα
Wang, N. S., McHeyzer‐Williams, L. J., Okitsu, S. L., Burris, T. P., Reiner, S. L., & McHeyzer‐Williams, M. G. (2012) · Nature Immunology · doi:10.1038/ni.2294 · Cited by 170
Kline, G. H., Hayden, T. A., & Klinman, N. R. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.6.3342 · Cited by 170
Tsukamoto, H., Clise-Dwyer, K., Huston, G. E., Duso, D. K., Buck, A. L., Johnson, L. L., Haynes, L., & Swain, S. L. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910139106 · Cited by 166 · cited 1×
“Thus, the renewal rates of both T and B cell pools decline (15, 20, 21), in part explaining how overall numbers can be maintained in the absence of newly generated cells.”
BackgroundVirally induced modulation of murine IgG antibody subclasses.
Coutelier, J. P., van der Logt, J. T. M., Heessen, F. W. A., Vink, A., & Snick, J. V. (1988) · The Journal of Experimental Medicine · doi:10.1084/jem.168.6.2373 · Cited by 160
Johnson, S. A., & Cambier, J. C. (2004) · Arthritis Research · doi:10.1186/ar1180 · Cited by 150
Labrie, J. E., Sah, A. P., Allman, D. M., Cancro, M. P., & Gerstein, R. M. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20040845 · Cited by 145
Self-citationStephan, R. P., Lill-Elghanian, D. A., & Witte, P. L. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.158.4.1598 · Cited by 133
T-bet regulates T-independent IgG2a class switching
Gerth, A. (2003) · International Immunology · doi:10.1093/intimm/dxg093 · Cited by 129
Stage-specific alterations in murine B lymphopoiesis with age
Stephan, R. P., Sanders, V. M., & Witte, P. L. (1996) · International Immunology · doi:10.1093/intimm/8.4.509 · Cited by 126
Giltiay, N., Chappell, C. P., Sun, X.-Z., Kolhatkar, N. S., Teal, T. H., Wiedeman, A., Kim, J., Tanaka, L., Buechler, M., Hamerman, J., et al. (2013) · Journal of Experimental Medicine · doi:10.1084/jem.20122798 · Cited by 116
The aged microenvironment contributes to the age-related functional defects of CD4 T cells in mice
Lefebvre, J. S., Maue, A. C., Eaton, S. M., Lanthier, P. A., Tighe, M., & Haynes, L. (2012) · Aging Cell · doi:10.1111/j.1474-9726.2012.00836.x · Cited by 103
B-cell depletion reactivates B lymphopoiesis in the BM and rejuvenates the B lineage in aging
Keren, Z., Naor, S., Nussbaum, S., Golan, K., Itkin, T., Sasaki, Y., Schmidt-Supprian, M., Lapidot, T., & Melamed, D. (2011) · Blood · doi:10.1182/blood-2010-09-307983 · Cited by 100
Age-Related Dysregulation in CD8 T Cell Homeostasis: Kinetics of a Diversity Loss
LeMaoult, J., Messaoudi, I., Manavalan, J. S., Potvin, H., Nikolich-Žugich, D., Dyall, R., Szabo, P., Weksler, M. E., & Nikolich‐Žugich, J. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.5.2367 · Cited by 96
Alterations in Marginal Zone Macrophages and Marginal Zone B Cells in Old Mice
Birjandi, S. Z., Ippolito, J. A., Ramadorai, A. K., & Witte, P. L. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1001271 · Cited by 92
Markine-Goriaynoff, D., & Coutelier, J. (2002) · Journal of Virology · doi:10.1128/jvi.76.1.432-435.2002 · Cited by 92
Yates, J. L., Racine, R., McBride, K. M., & Winslow, G. M. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1300062 · Cited by 90
Multiple prethymic defects underlie age-related loss of T progenitor competence
Zediak, V. P., Maillard, I., & Bhandoola, A. (2007) · Blood · doi:10.1182/blood-2007-01-071605 · Cited by 79
Immune Senescence: Mechanisms and Clinical Implications
Ben‐Yehuda, A., & Weksler, M. E. (1992) · Cancer Investigation · doi:10.3109/07357909209024815 · Cited by 68
Sherwood, E. M., Blomberg, B. B., Xu, W., Warner, C. A., & Riley, R. L. (1998) · PubMed · Cited by 62
Sherwood, E. M., Blomberg, B. B., Xu, W., Warner, C. A., & Riley, R. L. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.9.4472 · Cited by 59
Clonal expansions of B lymphocytes in old mice
LeMaoult, J., Delassus, S., Dyall, R., Nikolić‐Žugić, J., Kourilsky, P., & Weksler, M. E. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.159.8.3866 · Cited by 55
Genes, immunity, and senescence: looking for a link
Doria, G., & Frasca, D. (1997) · Immunological Reviews · doi:10.1111/j.1600-065x.1997.tb01036.x · Cited by 47
Memory B cells form in aged mice despite impaired affinity maturation and germinal center kinetics
Goenka, R., Scholz, J. L., Naradikian, M. S., & Cancro, M. P. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2013.12.013 · Cited by 38
Self-citationMurine gammaherpesvirus 68 infection protects lupus-prone mice from the development of autoimmunity
Larson, J. D., Thurman, J. M., Rubtsov, A. V., Claypool, D. J., Marrack, P., van Dyk, L. F., Torres, R. M., & Pelanda, R. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1203019109 · Cited by 35
Self-citationBassiri, A. E., Mandik‐Nayak, L., Seo, S.-J., Madaio, M. P., Cancro, M. P., & Erikson, J. (2000) · International Immunology · doi:10.1093/intimm/12.6.915 · Cited by 33
Self-citationCellular and molecular bases of B-cell clonal expansions.
Dolcetti, R., & Boiocchi, M. (1996) · PubMed · Cited by 31
Frasca, D., der Put, E. V., Riley, R. L., & Blomberg, B. B. (2004) · Experimental Gerontology · doi:10.1016/j.exger.2003.09.027 · Cited by 27
Immunosenescence and human longevity
Pawelec, G. (2003) · Biogerontology · doi:10.1023/a:1024185405946 · Cited by 16
Franceschi, C., Passeri, M., Benedictis, G. D., & Motta, L. (1998) · PubMed · Cited by 11
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Metadata
- Authors
- Rubtsova, K., Rubtsov, A. V., Cancro, M. P., & Marrack, P.
- Affiliations
- Howard Hughes Medical Institute (US)
- University of Pennsylvania (US)
- Corresponding author
- Rubtsova, Kira
- Marrack, Philippa
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-09-01
- Volume
- 195
- Issue
- 5
- Pages
- 1933-1937
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- PMC
- PMC4548292
- OpenAlex
- W2120679720
- Cited by
- 246
- References
- 57
- Citations by year
- 2026: 21 · 2025: 27 · 2024: 11 · 2023: 22 · 2022: 28 · 2021: 32 · 2020: 25 · 2019: 33 · 2018: 17 · 2017: 19 · 2016: 10 · 2015: 1
- FWCI
- 1.47
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute on Aging (R01AG-16841, R01AG016841)
- National Institute of Allergy and Infectious Diseases (AI-18785, T32AI074491, R37AI018785, R56AI018785, R01AI118691, R01AI018785)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- age-associated B cells, T-bet, B cell differentiation, aging, autoimmunity, viral infection, antibody response, B-cell origin, protective immunity
- MeSH terms
- T-bet Transcription Factor, Aging, Animals, Humans, Inflammation, Signal Transduction, Autoimmunity, B-Lymphocyte Subsets, Models, Immunological, T-Box Domain Proteins, Mice
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