title: Germinal center B cell depletion diminishes CD4+ follicular T helper cells in autoimmune mice.
abstract: BACKGROUND
  Continuous support from follicular CD4(+) T helper (Tfh) cells drives germinal center (GC) responses, which last for several weeks to produce high affinity memory B cells and plasma cells. In autoimmune Sle1 and NZB/W F1 mice, elevated numbers of Tfh cells persist, promoting the expansion of self-reactive B cells. Expansion of circulating Tfh like cells have also been described in several autoimmune diseases. Although, the signals required for Tfh differentiation have now been well described, the mechanisms that sustain the maintenance of fully differentiated Tfh are less understood. Recent data demonstrate a role for GC B cells for Tfh maintenance after protein immunization.
  
  
  RESULTS
  Given the pathogenic role Tfh play in autoimmune disease, we explored whether B cells are required for maintenance of autoreactive Tfh. Our data suggest that the number of mature autoreactive Tfh cells is controlled by GC B cells. Depletion of B cells in Sle1 autoimmune mice leads to a dramatic reduction in Tfh cells. In NZB/W F1 autoimmune mice, similar to the SRBC immunization model, GC B cells support the maintenance of mature Tfh, which is dependent mainly on ICOS. The CD28-associated pathway is dispensable for Tfh maintenance in SRBC immunized mice, but is required in the spontaneous NZB/W F1 model.
  
  
  CONCLUSIONS
  These data suggest that mature Tfh cells require signals from GC B cells to sustain their optimal numbers and function in both autoimmune and immunization models. Thus, immunotherapies targeting B cells in autoimmune disease may affect pathogenic Tfh cells.
authors.affiliation: Department of Respiratory, Inflammation and Autoimmunity Research, MedImmune LLC, Gaithersburg, Maryland, United States of America.
authors.forename: Isharat
authors.initials: I
authors.lastname: Yusuf
authors.affiliation: Department of Respiratory, Inflammation and Autoimmunity Research, MedImmune LLC, Gaithersburg, Maryland, United States of America.
authors.forename: Jessica
authors.initials: J
authors.lastname: Stern
authors.affiliation: Department of Respiratory, Inflammation and Autoimmunity Research, MedImmune LLC, Gaithersburg, Maryland, United States of America.
authors.forename: Tom M
authors.initials: TM
authors.lastname: McCaughtry
authors.affiliation: Department of Respiratory, Inflammation and Autoimmunity Research, MedImmune LLC, Gaithersburg, Maryland, United States of America.
authors.forename: Sandra
authors.initials: S
authors.lastname: Gallagher
authors.affiliation: Department of Respiratory, Inflammation and Autoimmunity Research, MedImmune LLC, Gaithersburg, Maryland, United States of America.
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Antibody Discovery and Protein Engineering, MedImmune LLC, Gaithersburg, Maryland, United States of America.
authors.forename: Changshou
authors.initials: C
authors.lastname: Gao
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Thomas
authors.initials: T
authors.lastname: Tedder
authors.affiliation: Department of Respiratory, Inflammation and Autoimmunity Research, MedImmune LLC, Gaithersburg, Maryland, United States of America.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Carlesso
authors.affiliation: Department of Respiratory, Inflammation and Autoimmunity Research, MedImmune LLC, Gaithersburg, Maryland, United States of America.
authors.forename: Laura
authors.initials: L
authors.lastname: Carter
authors.affiliation: Department of Respiratory, Inflammation and Autoimmunity Research, MedImmune LLC, Gaithersburg, Maryland, United States of America.
authors.forename: Ronald
authors.initials: R
authors.lastname: Herbst
authors.affiliation: Department of Respiratory, Inflammation and Autoimmunity Research, MedImmune LLC, Gaithersburg, Maryland, United States of America.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D002454:Cell Differentiation / Q000276:immunology; D018858:Germinal Center / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D018448:Models, Immunological; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology / Q000502:physiology*
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