Long-lived antigen-induced IgM plasma cells demonstrate somatic mutations and contribute to long-term protection.
Long-lived plasma cells are critical to humoral immunity as a lifelong source of protective antibodies. Antigen-activated B cells-with T-cell help-undergo affinity maturation within germinal centres and persist as long-lived IgG plasma cells in the bone marrow. Here we show that antigen-specific, induced IgM plasma cells also persist for a lifetime. Unlike long-lived IgG plasma cells, which develop in germinal centres and then home to the bone marrow, IgM plasma cells are primarily retained within the spleen and can develop even in the absence of germinal centres. Interestingly, their expressed IgV loci exhibit somatic mutations introduced by the activation-induced cytidine deaminase (AID). However, these IgM plasma cells are probably not antigen-selected, as replacement mutations are spread through the variable segment and not enriched within the CDRs. Finally, antibodies from long-lived IgM plasma cells provide protective host immunity against a lethal virus challenge.
Emory Vaccine Center, Yerkes National Primate Center, Emory University, 954 Gatewood Road Atlanta, Georgia 30329, USA.
Caitlin
C
Bohannon
Emory Vaccine Center, Yerkes National Primate Center, Emory University, 954 Gatewood Road Atlanta, Georgia 30329, USA.
Ryan
R
Powers
Emory Vaccine Center, Yerkes National Primate Center, Emory University, 954 Gatewood Road Atlanta, Georgia 30329, USA.
Lakshmipriyadarshini
L
Satyabhama
Interdepartmental Program in Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut 74085, USA.
Ang
A
Cui
Lowance Center for Human Immunology and Division of Rheumatology, Department of Medicine, Emory University, Atlanta, Georgia 30329, USA.
Christopher
C
Tipton
Computational Immunology Lab, The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel.
Miri
M
Michaeli
Emory Vaccine Center, Yerkes National Primate Center, Emory University, 954 Gatewood Road Atlanta, Georgia 30329, USA.
Ioanna
I
Skountzou
Emory Vaccine Center, Yerkes National Primate Center, Emory University, 954 Gatewood Road Atlanta, Georgia 30329, USA.
Robert S
RS
Mittler
Interdepartmental Program in Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut 74085, USA.|Department of Pathology, Yale University School of Medicine, Yale University, New Haven, Connecticut 74085, USA.|Department of Immunobiology, Yale University School of Medicine, Yale University, New Haven, Connecticut 74085, USA.
Steven H
SH
Kleinstein
Computational Immunology Lab, The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel.
Ramit
R
Mehr
Lowance Center for Human Immunology and Division of Rheumatology, Department of Medicine, Emory University, Atlanta, Georgia 30329, USA.
Frances Eun-Yun
FE
Lee
Lowance Center for Human Immunology and Division of Rheumatology, Department of Medicine, Emory University, Atlanta, Georgia 30329, USA.
Ignacio
I
Sanz
Emory Vaccine Center, Yerkes National Primate Center, Emory University, 954 Gatewood Road Atlanta, Georgia 30329, USA.
Joshy
J
Jacob
D019264:Adoptive Transfer; D020816:Amino Acid Motifs; D000818:Animals; D000941:Antigens / Q000276:immunology*; D022801:Complementarity Determining Regions / Q000235:genetics; D003564:Cytidine Deaminase / Q000737:chemistry / Q000235:genetics; D018858:Germinal Center / Q000166:cytology; D007109:Immunity; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007075:Immunoglobulin M / Q000276:immunology*; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics*; D009500:Neutralization Tests; D009975:Orthomyxoviridae / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000473:pathology / Q000821:virology; D010950:Plasma Cells / Q000276:immunology*; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics; D013154:Spleen / Q000166:cytology
D000941:Antigens; D022801:Complementarity Determining Regions; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D003564:Cytidine Deaminase