title: Further insights into the anti-PF4/heparin IgM immune response.
abstract: Anti-platelet factor 4 (PF4)/heparin antibodies are not only the cause of heparin-induced thrombocytopenia but might also play a role in the antibacterial host defence. Recently, marginal zone (MZ) B cells were identified to be crucial for anti-PF4/heparin IgG antibody production in mice. Combining human studies and a murine model of polymicrobial sepsis we further characterised the far less investigated anti-PF4/heparin IgM immune response. We detected anti-PF4/heparin IgM antibodies in the sera of paediatric patients < 6 months of age after cardiac surgery and in sera of splenectomised mice subjected to polymicrobial sepsis. In addition, PF4/heparin-specific IgM B cells were not only found in murine spleen, but also in peritoneum and bone marrow upon in vitro stimulation. Together, this indicates involvement of additional B cell populations, as MZ B cells are not fully developed in humans until the second year of life and are restricted to the spleen in mice. Moreover, PF4/heparin-specific B cells were detected in human cord blood upon in vitro stimulation and PF4-/- mice produced anti-PF4/heparin IgM antibodies after polymicrobial sepsis. In conclusion, the anti-PF4/heparin IgM response is a potential innate immune reaction driven by a B cell population distinct from MZ B cells.
authors.forename: Krystin
authors.initials: K
authors.lastname: Krauel
authors.forename: Annika
authors.initials: A
authors.lastname: Schulze
authors.forename: Rabie
authors.initials: R
authors.lastname: Jouni
authors.forename: Christine
authors.initials: C
authors.lastname: Hackbarth
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hietkamp
authors.forename: Sixten
authors.initials: S
authors.lastname: Selleng
authors.forename: Andreas
authors.initials: A
authors.lastname: Koster
authors.forename: Inga
authors.initials: I
authors.lastname: Jensch
authors.forename: Julia
authors.initials: J
authors.lastname: van der Linde
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Schwertz
authors.forename: Tamam
authors.initials: T
authors.lastname: Bakchoul
authors.forename: Matthias
authors.initials: M
authors.lastname: Hundt
authors.affiliation: Prof. Dr. Andreas Greinacher, Institut für Immunologie und Transfusionsmedizin, Universitätsmedizin Greifswald, Ferdinand-Sauerbruch-Strasse, D-17489 Greifswald, Germany, Tel.: +49 3834 865482, Fax: +49 3834 865489, E-mail: greinach@uni-greifswald.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Greinacher
mesh_terms: D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D060085:Coinfection / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007075:Immunoglobulin M / Q000097:blood*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010978:Platelet Factor 4 / Q000235:genetics / Q000276:immunology*; D018805:Sepsis / Q000276:immunology*; D013921:Thrombocytopenia / Q000139:chemically induced / Q000276:immunology*
chemical_list: D007075:Immunoglobulin M; D010978:Platelet Factor 4
keywords: B cells; HIT; anti-PF4/heparin antibodies; immune response