Abstract
The tonsils provide defense of the upper aerodigestive tract against pathogens. Although long known to undergo functional changes with age, the precise changes occurring within tonsillar B cell populations remain undefined. In the present study, we investigated age-related changes in palatine tonsillar B cell subsets and immunoglobulin (Ig) isotypes. Palatine tonsils were obtained from forty-two tonsillectomy patients without tonsillitis who were divided into three groups: young children (4–9 years), adolescents (10–19 years), and adults (20–60 years). Tonsillar B cells were then analyzed by flow cytometry. Using expression of CD38 and IgD to define B cell subsets, we found that the frequency of germinal center (GC) B cells in the tonsils was significantly higher, and the frequency of memory B cells lower, in young children as compared to adolescents and adults. Within the GC B cell subsets, adults had a higher frequency of IgA+ cells and a lower frequency of IgM+ cells as compared to individuals in the younger age groups. Moreover, young children had a higher frequency of IgG+ cells in the GC B cell subsets than did individuals in the older age groups. We also observed an abundance of IgM+ cells among memory B cells and plasmablasts in young children and IgA+ cells in adults. In summary, the proportion of GC B cells in palatine tonsillar B cells decreases with age, while the proportion of memory B cells increases with age. In addition, Ig isotypes in tonsils preferentially switch from IgM to IgA as individuals age.
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Abbreviations
- GC:
-
Germinal center
- Ig:
-
Immunoglobulin
- MFI:
-
Mean fluorescence intensity
References
Surjan L Jr. Tonsils and lympho-epithelial structures in the pharynx as immuno-barriers. Acta Otolaryngol. 1987;103:369.
Brandtzaeg P. Immunobarriers of the mucosa of the upper respiratory and digestive pathways. Acta Otolaryngol. 1988;105:172.
Korsrud FR, Brandtzaeg P. Immune systems of human nasopharyngeal and palatine tonsils: histomorphometry of lymphoid components and quantification of immunoglobulin-producing cells in health and disease. Clin Exp Immunol. 1980;39:361.
Brandtzaeg P. Immunology of tonsils and adenoids: everything the ENT surgeon needs to know. Int J Pediatr Otorhinolaryngol. 2003;67(Suppl 1):S69.
Van Kempen MJ, Rijkers GT, Van Cauwenberge PB. The immune response in adenoids and tonsils. Int Arch Allergy Immunol. 2000;122:8.
Quiding-Jarbrink M, Granstrom G, Nordstrom I, Holmgren J, Czerkinsky C. Induction of compartmentalized B-cell responses in human tonsils. Infect Immun. 1995;63:853.
Wilson S, Norton P, Haverson K, Leigh J, Bailey M. Development of the palatine tonsil in conventional and germ-free piglets. Dev Comp Immunol. 2005;29:977.
Akcay A, Kara CO, Dagdeviren E, Zencir M. Variation in tonsil size in 4- to 17-year-old schoolchildren. J Otolaryngol. 2006;35:270.
Papaioannou G, Kambas I, Tsaoussoglou M, Panaghiotopoulou-Gartagani P, Chrousos G, Kaditis AG. Age-dependent changes in the size of adenotonsillar tissue in childhood: implications for sleep-disordered breathing. J Pediatr. 2013;162:269.
Sanz I, Wei C, Lee FE, Anolik J. Phenotypic and functional heterogeneity of human memory B cells. Semin Immunol. 2008;20(1):67–82.
Liu YJ, Arpin C. Germinal center development. Immunol Rev. 1997;156:111–26.
Choi YS. Differentiation and apoptosis of human germinal center B-lymphocytes. Immunol Res. 1997;16(2):161–74.
Mattila PS, Tarkkanen J. Age-associated changes in the cellular composition of the human adenoid. Scand J Immunol. 1997;45(4):423–7.
Kolar GR, Mehta D, Wilson PC, Capra JD. Diversity of the Ig repertoire is maintained with age in spite of reduced germinal centre cells in human tonsil lymphoid tissue. Scand J Immunol. 2006;64(3):314–24.
Gonzalez-Garcia I, Ocana E, Jimenez-Gomez G, Campos-Caro A, Brieva JA. Immunization-induced perturbation of human blood plasma cell pool: progressive maturation, IL-6 responsiveness, and high PRDI-BF1/BLIMP1 expression are critical distinctions between antigen-specific and nonspecific plasma cells. J Immunol. 2006;176(7):4042–50.
Dorner T, Radbruch A. Antibodies and B cell memory in viral immunity. Immunity. 2007;27(3):384–92.
Valles-Ayoub Y, Govan HL III, Braun J. Evolving abundance and clonal pattern of human germinal center B cells during childhood. Blood. 1990;76(1):17–23.
Yamanaka N, Matsuyama H, Harabuchi Y, Kataura A. Distribution of lymphoid cells in tonsillar compartments in relation to infection and age. A quantitative study using image analysis. Acta Otolaryngol. 1992;112(1):128–37.
McDonald KG, Leach MR, Huang C, Wang C, Newberry RD. Aging impacts isolated lymphoid follicle development and function. Immun Ageing. 2011;8(1):1.
Bourges D, Wang CH, Chevaleyre C, Salmon H. T and IgA B lymphocytes of the pharyngeal and palatine tonsils: differential expression of adhesion molecules and chemokines. Scand J Immunol. 2004;60(4):338–50.
Paganelli R, Scala E, Quinti I, Ansotegui IJ. Humoral immunity in aging. Aging Clin Exp Res. 1994;6(3):143–50.
McDonald KG, McDonough JS, Dieckgraefe BK, Newberry RD. Dendritic cells produce CXCL13 and participate in the development of murine small intestine lymphoid tissues. Am J Pathol. 2010;176(5):2367–77.
Ansel KM, Ngo VN, Hyman PL, Luther SA, Forster R, Sedgwick JD, Browning JL, Lipp M, Cyster JG. A chemokine-driven positive feedback loop organizes lymphoid follicles. Nature. 2000;406(6793):309–14.
Velaga S, Herbrand H, Friedrichsen M, Jiong T, Dorsch M, Hoffmann MW, Förster R, Pabst O. Chemokine receptor CXCR5 supports solitary intestinal lymphoid tissue formation, B cell homing, and induction of intestinal IgA responses. J Immunol. 2009;182(5):2610–9.
Kunkel EJ, Campbell DJ, Butcher EC. Chemokines in lymphocyte trafficking and intestinal immunity. Microcirculation. 2003;10(3–4):313–23.
McDonald KG, McDonough JS, Wang C, Kucharzik T, Williams IR, Newberry RD. CC chemokine receptor 6 expression by B lymphocytes is essential for the development of isolated lymphoid follicles. Am J Pathol. 2007;170(4):1229–40.
Ogra PL. Effect of tonsillectomy and adenoidectomy on nasopharyngeal antibody response to poliovirus. N Engl J Med. 1971;284(2):59–64.
Cantani A, Bellioni P, Salvinelli F, Businco L. Serum immunoglobulins and secretory IgA deficiency in tonsillectomized children. Ann Allergy. 1986;57(6):413–6.
D’Amelio R, Palmisano L, Le Moli S, Seminara R, Aiuti F. Serum and salivary IgA levels in normal subjects: comparison between tonsillectomized and non-tonsillectomized subjects. Int Arch Allergy Appl Immunol. 1982;68(3):256–9.
Lenander-Lumikari M, Tenovuo J, Puhakka HJ, Malvaranta T, Ruuskanen O, Meurman O, Meurman P, Vilja P. Salivary antimicrobial proteins and mutans streptococci in tonsillectomized children. Pediatr Dent. 1992;14(2):86–91.
Childers NK, Powell WD, Tong G, Kirk K, Wiatrak B, Michalek SM. Human salivary immunoglobulin and antigen-specific antibody activity after tonsillectomy. Oral Microbiol Immunol. 2001;16(5):265–9.
Ikinciogullari A, Dogu F, Ikinciogullari A, Egin Y, Babacan E. Is immune system influenced by adenotonsillectomy in children? Int J Pediatr Otorhinolaryngol. 2002;66(3):251–7.
Van den Akker EH, Sanders EA, van Staaij BK, Rijkers GT, Rovers MM, Hoes AW, Schilder AG. Long-term effects of pediatric adenotonsillectomy on serum immunoglobulin levels: results of a randomized controlled trial. Ann Allergy Asthma Immunol. 2006;97(2):251–6.
Acknowledgments
This work was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health and Welfare, Korea (HI13C1263). This work was also supported by National Research Foundation grants (2012-M3C1A1-048860 and 2014R1A1A1005598) and the Korea Advanced Institute of Science and Technology (KAIST) Future Systems Healthcare Project funded by the Ministry of Science, ICT and Future Planning of Korea.
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The authors have no conflicting financial interests.
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Jino Lee and Dong-Yeop Chang have contributed equally to this work.
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Lee, J., Chang, DY., Kim, SW. et al. Age-related differences in human palatine tonsillar B cell subsets and immunoglobulin isotypes. Clin Exp Med 16, 81–87 (2016). https://doi.org/10.1007/s10238-015-0338-5
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DOI: https://doi.org/10.1007/s10238-015-0338-5