Krauel Krystin, Schulze Annika, Jouni Rabie, Hackbarth Christine, Hietkamp Bernhard, Selleng Sixten, Koster Andreas, Jensch Inga, van der Linde Julia, Schwertz Hansjörg, Bakchoul Tamam, Hundt Matthias, Greinacher Andreas
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:
Thromb Haemost. 2016 Apr;115(4):752-61. doi: 10.1160/TH15-08-0654. Epub 2015 Oct 15.
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.
抗血小板因子4（PF4）/肝素抗体不仅是肝素诱导的血小板减少症的病因，还可能在抗菌宿主防御中发挥作用。最近，边缘区（MZ）B细胞被确定为小鼠抗PF4/肝素IgG抗体产生的关键因素。结合人体研究和多微生物败血症的小鼠模型，我们进一步对研究较少的抗PF4/肝素IgM免疫反应进行了表征。我们在心脏手术后6个月以下儿科患者的血清以及接受多微生物败血症的脾切除小鼠的血清中检测到了抗PF4/肝素IgM抗体。此外，PF4/肝素特异性IgM B细胞不仅在小鼠脾脏中发现，体外刺激后在腹膜和骨髓中也有发现。总之，这表明还有其他B细胞群体参与其中，因为MZ B细胞在人类直到两岁才完全发育，在小鼠中则局限于脾脏。此外，体外刺激后人脐血中检测到PF4/肝素特异性B细胞，多微生物败血症后PF4基因敲除小鼠产生了抗PF4/肝素IgM抗体。总之，抗PF4/肝素IgM反应是一种由不同于MZ B细胞的B细胞群体驱动的潜在先天免疫反应。
