title: Human B cells have an active phagocytic capability and undergo immune activation upon phagocytosis of Mycobacterium tuberculosis.
abstract: The paradigm that B cells are nonphagocytic was taken for granted for a long time until phagocytic B cells were found in early vertebrate animals. Thereafter, limited evidence has shown that human B cells may also internalize bacteria. However, whether human B cells can actively phagocytose bacteria has been less extensively investigated; in particular, the mechanisms and significance of the phagocytosis require clarification. Here, we show that the human Raji B cell line can phagocytose both live and dead Mycobacterium tuberculosis (Mtb), and the phagocytosed Mtb in turn affects the immune functions of the B cells. After incubation of Raji cells with Mtb, our confocal microscopy, electron microscopy and flow cytometry data showed that Raji cells effectively engulfed Mtb as well as latex beads. The phagocytic rate was proportional to the incubation time and the amount of Mtb or beads added. Additionally, we found that normal human serum could enhance the ability of Raji cells to phagocytose Mtb, while heat-inactivated serum reversed this promoting effect. The phagocytic process of B cells could partially be inhibited by cytochalasin B, an actin inhibitor. Importantly, the phagocytosed Mtb could regulate B cell immune functions, such as stimulating IgM production and upregulating the expression of the antigen-presenting costimulatory molecules CD80 and CD86. Therefore, our results provide the first evidence that human B cells can phagocytose Mtb in an active manner that is independent of bacterial viability, and phagocytosed Mtb can in turn regulate the immune activation of B cells.
authors.affiliation: Department of Neurology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China; Department of Neurology, Wuhan General Hospital of Guangzhou Military, Wuhan, Hubei, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Fuzhou Dongfang Hospital, Fuzhou, Fujian, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Shi
authors.affiliation: Department of Neurology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China; Department of Neurology, The PLA 153 Hospital, Zhengzhou, Henan, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Neurology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Guangyun
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China; Department of Neurology, The First Hospital Affiliated to Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China.
authors.forename: Longxiu
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Neurology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China; Department of Neurology, The First People's Hospital of Xi'an City, Xi'an, Shaanxi, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhi
authors.affiliation: Department of Neurology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Gengyao
authors.initials: G
authors.lastname: Hu
authors.affiliation: Department of Neurology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Pin
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Neurology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Yining
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Neurology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Dai
authors.affiliation: Department of Neurology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Neurology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Neurology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China. Electronic address: fgd2000@163.com.
authors.forename: Guodong
authors.initials: G
authors.lastname: Feng
authors.affiliation: Department of Neurology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China. Electronic address: zhaogang@fmmu.edu.cn.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhao
mesh_terms: D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000648:ultrastructure; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology; D051940:B7-2 Antigen / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D003571:Cytochalasin B / Q000494:pharmacology*; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D006801:Humans; D007075:Immunoglobulin M / Q000235:genetics; D008213:Lymphocyte Activation / Q000187:drug effects*; D008863:Microspheres; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000276:immunology* / Q000648:ultrastructure; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology*; D015398:Signal Transduction
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D007075:Immunoglobulin M; D003571:Cytochalasin B
keywords: Human B cells; Immune response; Mycobacterium tuberculosis; Phagocytosis; Raji cells