title: Distinct T helper cell dependence of memory B-cell proliferation versus plasma cell differentiation.
abstract: Several memory B-cell subclasses with distinct functions have been described, of which the most effective is the class-switched (CS) memory B-cell population. We have previously shown, using virus-like particles (VLPs), that the proliferative potential of these CS memory B cells is limited and they fail to re-enter germinal centres (GCs). However, VLP-specific memory B cells quickly differentiated into secondary plasma cells (PCs) with the virtue of elevated antibody production compared with primary PCs. Whereas the induction of VLP+memory B cells was strongly dependent on T helper cells, we were wondering whether re-stimulation of VLP+memory B cells and their differentiation into secondary PCs would also require T helper cells. Global absence of T helper cells led to strongly impaired memory B cell proliferation and PC differentiation. In contrast, lack of interleukin-21 receptor-dependent follicular T helper cells or CD40 ligand signalling strongly affected proliferation of memory B cells, but differentiation into mature secondary PCs exhibiting increased antibody production was essentially normal. This contrasts with primary B-cell responses, where a strong dependence on CD40 ligand but limited importance of interleukin-21 receptor was seen. Hence, T helper cell dependence differs between primary and secondary B-cell responses as well as between memory B-cell proliferation and PC differentiation.
authors.affiliation: Department of Dermatology, Zurich University Hospital, Schlieren/Zurich, Switzerland.
authors.forename: Franziska
authors.initials: F
authors.lastname: Zabel
authors.affiliation: Department of Dermatology, Zurich University Hospital, Schlieren/Zurich, Switzerland.
authors.forename: Antonia
authors.initials: A
authors.lastname: Fettelschoss
authors.affiliation: Inselspital, Department of Immunology, University of Bern, Bern, Switzerland.
authors.forename: Monique
authors.initials: M
authors.lastname: Vogel
authors.affiliation: Department of Dermatology, Zurich University Hospital, Zurich, Switzerland.
authors.forename: Pål
authors.initials: P
authors.lastname: Johansen
authors.affiliation: Department of Dermatology, Zurich University Hospital, Zurich, Switzerland.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Kündig
authors.affiliation: Department of Dermatology, Zurich University Hospital, Schlieren/Zurich, Switzerland.|Inselspital, Department of Immunology, University of Bern, Bern, Switzerland.
authors.forename: Martin F
authors.initials: MF
authors.lastname: Bachmann
mesh_terms: D000818:Animals; D000917:Antibody Formation; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D023201:CD40 Ligand / Q000235:genetics; D002454:Cell Differentiation; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D007156:Immunologic Memory / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010950:Plasma Cells / Q000276:immunology*; D053655:Receptors, Interleukin-21 / Q000235:genetics; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D016207:Cytokines; D053655:Receptors, Interleukin-21; D023201:CD40 Ligand
keywords: T helper cell-dependent immune response; antibodies; memory B cells; plasma cell differentiation; secondary response