title: IL-21 receptor is critical for the development of memory B cell responses.
abstract: Development of long-term humoral immunity, characterized by the formation of long-lived plasma cells (PCs) in the bone marrow and memory B cells, is a critical component of protective immunity to pathogens, and as such it is the major goal of vaccination. However, the mechanisms involved in the generation of long-term humoral immunity remain poorly understood. In this study, we used IL-21R-deficient (IL-21R.KO) mice to examine the role of the IL-21 pathway in the development of the B cell memory response. Primary IgG serum Ab responses to the T cell-dependent Ag 4-hydroxy-3-nitrophenylacetyl (NP) hapten conjugated to chicken γ globulin were delayed in IL-21R.KO mice, but reached normal titers within 3 to 4 wk of immunization. IL-21R.KO mice formed germinal centers and generated normal numbers of PCs in their bone marrow. Additionally, memory B cell formation was similar in wild-type and IL-21R.KO mice. However, NP-specific memory B cells and PCs failed to expand following secondary immunization of IL-21R.KO mice, and consequently, secondary IgG Ab responses to NP hapten conjugated to chicken γ globulin were significantly impaired. These results identify the IL-21 pathway as a critical component of the memory B cell response.
authors.affiliation: Inflammation and Immunology, Pfizer Research, Cambridge, MA 02140, USA.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Rankin
authors.forename: Heather
authors.initials: H
authors.lastname: MacLeod
authors.forename: Sean
authors.initials: S
authors.lastname: Keegan
authors.forename: Tatyana
authors.initials: T
authors.lastname: Andreyeva
authors.forename: Leslie
authors.initials: L
authors.lastname: Lowe
authors.forename: Laird
authors.initials: L
authors.lastname: Bloom
authors.forename: Mary
authors.initials: M
authors.lastname: Collins
authors.forename: Cheryl
authors.initials: C
authors.lastname: Nickerson-Nutter
authors.forename: Deborah
authors.initials: D
authors.lastname: Young
authors.forename: Heath
authors.initials: H
authors.lastname: Guay
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000096:biosynthesis; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002645:Chickens / Q000276:immunology; D020566:Dendritic Cells, Follicular / Q000276:immunology / Q000378:metabolism; D018858:Germinal Center / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006241:Haptens / Q000008:administration & dosage / Q000276:immunology; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007075:Immunoglobulin M / Q000096:biosynthesis*; D007156:Immunologic Memory / Q000235:genetics / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009596:Nitrophenols / Q000008:administration & dosage / Q000276:immunology; D010648:Phenylacetates / Q000008:administration & dosage / Q000276:immunology; D061026:Programmed Cell Death 1 Receptor; D054380:Receptors, CXCR5 / Q000096:biosynthesis; D053655:Receptors, Interleukin-21 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005719:gamma-Globulins / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; C513179:CXCR5 protein, mouse; D006241:Haptens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D009596:Nitrophenols; C491383:Pdcd1 protein, mouse; D010648:Phenylacetates; D061026:Programmed Cell Death 1 Receptor; D054380:Receptors, CXCR5; D053655:Receptors, Interleukin-21; D005719:gamma-Globulins; C026242:4-hydroxy-5-nitrophenyl acetic acid; D017493:Leukocyte Common Antigens