title: BLyS inhibition eliminates primary B cells but leaves natural and acquired humoral immunity intact.
abstract: We have used an inhibiting antibody to determine whether preimmune versus antigen-experienced B cells differ in their requisites for BLyS, a cytokine that controls differentiation and survival. Whereas in vivo BLyS inhibition profoundly reduced naïve B cell numbers and primary immune responses, it had a markedly smaller effect on memory B cells and long-lived plasma cells, as well as secondary immune responses. There was heterogeneity within the memory pools, because IgM-bearing memory cells were sensitive to BLyS depletion whereas IgG-bearing memory cells were not, although both were more resistant than naïve cells. There was also heterogeneity within B1 pools, as splenic but not peritoneal B1 cells were diminished by anti-BLyS treatment, yet the number of natural antibody-secreting cells remained constant. Together, these findings show that memory B cells and natural antibody-secreting cells are BLyS-independent and suggest that these pools can be separately manipulated.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6082, USA.
authors.forename: Jean L
authors.initials: JL
authors.lastname: Scholz
authors.forename: Jenni E
authors.initials: JE
authors.lastname: Crowley
authors.forename: Mary M
authors.initials: MM
authors.lastname: Tomayko
authors.forename: Natalie
authors.initials: N
authors.lastname: Steinel
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: O'Neill
authors.forename: William J
authors.initials: WJ
authors.lastname: Quinn
authors.forename: Radhika
authors.initials: R
authors.lastname: Goenka
authors.forename: Juli P
authors.initials: JP
authors.lastname: Miller
authors.forename: Yun Hee
authors.initials: YH
authors.lastname: Cho
authors.forename: Vatana
authors.initials: V
authors.lastname: Long
authors.forename: Chris
authors.initials: C
authors.lastname: Ward
authors.forename: Thi-Sau
authors.initials: TS
authors.lastname: Migone
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Shlomchik
authors.forename: Michael P
authors.initials: MP
authors.lastname: Cancro
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D053264:B-Cell Activating Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D005260:Female; D007113:Immunity, Innate / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D053264:B-Cell Activating Factor