title: Interaction of SIGNR1 expressed by marginal zone macrophages with marginal zone B cells is essential to early IgM responses against Streptococcus pneumoniae.
abstract: The spleen plays a pivotal role in the immune defense against encapsulated bacteria such as Streptococcus pneumoniae. Murine splenic marginal zone macrophages express the C-type lectin SIGNR1, which is crucial for the capture of S. pneumoniae from blood. In this study, we demonstrate that SIGNR1 is able to interact in vitro with the juxtaposing marginal zone B cell population, which is responsible for the production of the early IgM response against the S. pneumoniae-epitope phosphorylcholine. Strikingly, SIGNR1-deficient mice display a reduction in the marginal zone B cell population. In addition, ex vivo B cell stimulation assays demonstrate a decrease in phosphorylcholine specificity in the splenic B cell population derived from SIGNR1-deficient mice, whereas the total IgM response is unaffected. Therefore, we hypothesize that antigens are presented by SIGNR1 expressed by marginal zone macrophages to the developing marginal zone B cell population thereby influencing the repertoire of this B cell population, which is pivotal for the early immune response against encapsulated bacteria such as S. pneumoniae.
authors.affiliation: Department of Molecular Cell Biology & Immunology, VU University Medical Center Amsterdam, v.d. Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
authors.forename: Estella A
authors.initials: EA
authors.lastname: Koppel
authors.forename: Manja
authors.initials: M
authors.lastname: Litjens
authors.forename: Venice C
authors.initials: VC
authors.lastname: van den Berg
authors.forename: Yvette
authors.initials: Y
authors.lastname: van Kooyk
authors.forename: Teunis B H
authors.initials: TB
authors.lastname: Geijtenbeek
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000382:microbiology*; D017848:Blood-Borne Pathogens; D016466:CHO Cells; D015815:Cell Adhesion Molecules / Q000172:deficiency / Q000276:immunology*; D002452:Cell Count; D006224:Cricetinae; D003412:Cricetulus; D007075:Immunoglobulin M / Q000276:immunology*; D037181:Lectins, C-Type / Q000172:deficiency / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D010713:Phosphatidylcholines / Q000276:immunology; D011135:Polysaccharides, Bacterial / Q000276:immunology; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D007075:Immunoglobulin M; D037181:Lectins, C-Type; D010713:Phosphatidylcholines; D011135:Polysaccharides, Bacterial; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin