title: B cell antigen receptors of the IgM and IgD classes are clustered in different protein islands that are altered during B cell activation.
abstract: The B cell antigen receptors (BCRs) play an important role in the clonal selection of B cells and their differentiation into antibody-secreting plasma cells. Mature B cells have both immunoglobulin M (IgM) and IgD types of BCRs, which have identical antigen-binding sites and are both associated with the signaling subunits Igα and Igβ, but differ in their membrane-bound heavy chain isoforms. By two-color direct stochastic optical reconstruction microscopy (dSTORM), we showed that IgM-BCRs and IgD-BCRs reside in the plasma membrane in different protein islands with average sizes of 150 and 240 nm, respectively. Upon B cell activation, the BCR protein islands became smaller and more dispersed such that the IgM-BCRs and IgD-BCRs were found in close proximity to each other. Moreover, specific stimulation of one class of BCR had minimal effects on the organization of the other. These conclusions were supported by the findings from two-marker transmission electron microscopy and proximity ligation assays. Together, these data provide evidence for a preformed multimeric organization of BCRs on the plasma membrane that is remodeled after B cell activation.
authors.affiliation: BIOSS Centre for Biological Signalling Studies, University of Freiburg, D-79104 Freiburg, Germany. Department of Molecular Immunology, Institute of Biology III at the Faculty of Biology of the University of Freiburg, D-79104, and at the Max Planck Institute of Immunobiology and Epigenetics, D-79108 Freiburg, Germany. maity@ie-freiburg.mpg.de michael.reth@bioss.uni-freiburg.de.
authors.forename: Palash Chandra
authors.initials: PC
authors.lastname: Maity
authors.affiliation: Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Blount
authors.affiliation: Department of Molecular Immunology, Institute of Biology III at the Faculty of Biology of the University of Freiburg, D-79104, and at the Max Planck Institute of Immunobiology and Epigenetics, D-79108 Freiburg, Germany. Institute of Immunology, Ulm University, D-89081 Ulm, Germany.
authors.forename: Hassan
authors.initials: H
authors.lastname: Jumaa
authors.affiliation: BIOSS Centre for Biological Signalling Studies, University of Freiburg, D-79104 Freiburg, Germany. Institute of Computer Science, University of Freiburg, D-79110 Freiburg Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Ronneberger
authors.affiliation: Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Björn F
authors.initials: BF
authors.lastname: Lillemeier
authors.affiliation: BIOSS Centre for Biological Signalling Studies, University of Freiburg, D-79104 Freiburg, Germany. Department of Molecular Immunology, Institute of Biology III at the Faculty of Biology of the University of Freiburg, D-79104, and at the Max Planck Institute of Immunobiology and Epigenetics, D-79108 Freiburg, Germany. maity@ie-freiburg.mpg.de michael.reth@bioss.uni-freiburg.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Reth
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002462:Cell Membrane / Q000235:genetics / Q000276:immunology*; D007072:Immunoglobulin D / Q000235:genetics / Q000276:immunology*; D007075:Immunoglobulin M / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology*
chemical_list: D007072:Immunoglobulin D; D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell