title: Imprinting the fate of antigen-reactive B cells through the affinity of the B cell receptor.
abstract: Long-lived plasma cells (PCs) and memory B cells (B(mem)) constitute the cellular components of enduring humoral immunity, whereas short-lived PCs that rapidly produce Ig correspond to the host's need for immediate protection against pathogens. In this study we show that the innate affinity of the BCR for Ag imprints upon naive B cells their differentiation fate to become short- or long-lived PCs and B(mem). Using BCR transgenic mice with varying affinities for Ag, naive B cells with high affinity lose their capacity to form germinal centers (GCs), develop neither B(mem) nor long-lived PCs, and are destined to a short-lived PC fate. Moderate affinity interactions result in hastened GC responses, and differentiation to long-lived PCs, but B(mem) remain extinct. In contrast, lower affinity interactions show tempered GCs, producing B(mem) and affinity-matured, long-lived PCs. Thus, a continuum of elementary to comprehensive humoral immune responses exists that is controlled by inherent BCR affinity.
authors.affiliation: Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH 03756, USA.
authors.forename: Brian P
authors.initials: BP
authors.lastname: O'Connor
authors.forename: Laura A
authors.initials: LA
authors.lastname: Vogel
authors.forename: Weijun
authors.initials: W
authors.lastname: Zhang
authors.forename: William
authors.initials: W
authors.lastname: Loo
authors.forename: Danielle
authors.initials: D
authors.lastname: Shnider
authors.forename: Evan F
authors.initials: EF
authors.lastname: Lind
authors.forename: Michelle
authors.initials: M
authors.lastname: Ratliff
authors.forename: Randolph J
authors.initials: RJ
authors.lastname: Noelle
authors.forename: Loren D
authors.initials: LD
authors.lastname: Erickson
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000915:Antibody Affinity / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D018858:Germinal Center / Q000276:immunology; D007091:Image Processing, Computer-Assisted; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D011947:Receptors, Antigen, B-Cell