title: Tissue distribution and dependence of responsiveness of human antigen-specific memory B cells.
abstract: Memory B cells (mBCs) are a key to immunologic memory, yet their distribution within lymphoid organs and the individual role of these for mBC functionality remain largely unknown. This study characterized the distribution and phenotype of human (Ag-specific) mBCs in peripheral blood (PB), spleen, tonsil, and bone marrow. We found that the spleen harbors most mBCs, followed by tonsils, BM, and PB, and we detected no major differences in expression of markers associated with higher maturity. Testing the distribution of tetanus toxoid-specific (TT(+)) mBCs revealed their presence in PB during steady state, yet absolute numbers suggested their largest reservoir in the spleen, followed by tonsils. To explore the role of both tissues in the maintenance of reactive B cell memory, we revaccinated controls and splenectomized and tonsillectomized individuals with TT. All donor groups exhibited comparable emergence of anti-TT IgG, TT(+) plasma cells, and TT(+) mBCs in the PB, together with similar molecular characteristics of TT(+) plasma cells. In summary, human mBCs recirculate through PB and reside in different lymphoid organs that do not reflect different mBC maturity stages. The spleen and tonsil, although harboring the largest number of overall and TT(+) mBCs, appear to be dispensable to preserve adequate responsiveness to secondary antigenic challenge.
authors.affiliation: Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie, Charite Universitätsmedizin Berlin, 10117 Berlin, Germany;
authors.forename: Claudia
authors.initials: C
authors.lastname: Giesecke
authors.forename: Daniela
authors.initials: D
authors.lastname: Frölich
authors.forename: Karin
authors.initials: K
authors.lastname: Reiter
authors.forename: Henrik E
authors.initials: HE
authors.lastname: Mei
authors.forename: Ina
authors.initials: I
authors.lastname: Wirries
authors.forename: Rainer
authors.initials: R
authors.lastname: Kuhly
authors.forename: Monica
authors.initials: M
authors.lastname: Killig
authors.forename: Timor
authors.initials: T
authors.lastname: Glatzer
authors.forename: Katharina
authors.initials: K
authors.lastname: Stölzel
authors.forename: Carsten
authors.initials: C
authors.lastname: Perka
authors.forename: Peter E
authors.initials: PE
authors.lastname: Lipsky
authors.forename: Thomas
authors.initials: T
authors.lastname: Dörner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000941:Antigens / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001853:Bone Marrow / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D014066:Palatine Tonsil / Q000276:immunology*; D010950:Plasma Cells / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism; D013154:Spleen / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology; D055815:Young Adult
chemical_list: D000941:Antigens; D015703:Antigens, CD; D007074:Immunoglobulin G; D011947:Receptors, Antigen, B-Cell; D013745:Tetanus Toxoid