title: A germinal center-independent pathway generates unswitched memory B cells early in the primary response.
abstract: Memory B cells can be produced from the classical germinal center (GC) pathway or a less understood GC-independent route. We used antigen-based cell enrichment to assess the relative contributions of these pathways to the polyclonal memory B cell pool. We identified a CD38(+) GL7(+) B cell precursor population that differentiated directly into IgM(+) or isotype-switched (sw) Ig(+) memory B cells in a GC-independent fashion in response to strong CD40 stimulation. Alternatively, CD38(+) GL7(+) B cell precursors had the potential to become Bcl-6(+) GC cells that then generated primarily swIg(+) memory B cells. These results demonstrate that early IgM(+) and swIg(+) memory B cells are products of a GC-independent pathway, whereas later switched Ig(+) memory B cells are products of GC cells.
authors.affiliation: Department of Microbiology, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. TAYL0611@umn.edu
authors.forename: Justin J
authors.initials: JJ
authors.lastname: Taylor
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Pape
authors.forename: Marc K
authors.initials: MK
authors.lastname: Jenkins
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism; D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D019013:CD40 Antigens / Q000008:administration & dosage; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D005260:Female; D018858:Germinal Center / Q000276:immunology; D007156:Immunologic Memory; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D039902:Multipotent Stem Cells / Q000276:immunology; D010641:Phenotype; D051560:Proto-Oncogene Proteins c-bcl-6; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology
chemical_list: D000943:Antigens, Differentiation; C490010:Bcl6 protein, mouse; D019013:CD40 Antigens; D004268:DNA-Binding Proteins; D008562:Membrane Glycoproteins; D051560:Proto-Oncogene Proteins c-bcl-6; D011947:Receptors, Antigen, B-Cell; C096712:antigen GL7; D015720:5'-Nucleotidase; C498155:Cd38 protein, mouse; D051997:ADP-ribosyl Cyclase 1