Missing-in-Metastasis/Metastasis Suppressor 1 Regulates B Cell Receptor Signaling, B Cell Metabolic Potential, and T Cell-Independent Immune Responses.

Alexey V Sarapulov, Petar Petrov, Sara Hernández-Pérez, Vid Šuštar, Elina Kuokkanen, Lena Cords, Rufus V M Samuel, Marika Vainio, Marco Fritzsche, Yolanda R Carrasco, Pieta K Mattila

Frontiers in immunology 2020

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Efficient generation of antibodies by B cells is one of the prerequisites of protective immunity. B cell activation by cognate antigens via B cell receptors (BCRs), or pathogen-associated molecules through pattern-recognition receptors, such as Toll-like receptors (TLRs), leads to transcriptional and metabolic changes that ultimately transform B cells into antibody-producing plasma cells or memory cells. BCR signaling and a number of steps downstream of it rely on coordinated action of cellular membranes and the actin cytoskeleton, tightly controlled by concerted action of multiple regulatory proteins, some of them exclusive to B cells. Here, we dissect the role of Missing-In-Metastasis (MIM), or Metastasis suppressor 1 (MTSS1), a cancer-associated membrane and actin cytoskeleton regulating protein, in B cell-mediated immunity by taking advantage of MIM knockout mouse strain. We show undisturbed B cell development and largely normal composition of B cell compartments in the periphery. Interestingly, we found that MIM-/- B cells are defected in BCR signaling in response to surface-bound antigens but, on the other hand, show increased metabolic activity after stimulation with LPS or CpG. In vivo, MIM knockout animals exhibit impaired IgM antibody responses to immunization with T cell-independent antigen. This study provides the first comprehensive characterization of MIM in B cells, demonstrates its regulatory role for B cell-mediated immunity, as well as proposes new functions for MIM in tuning receptor signaling and cellular metabolism, processes, which may also contribute to the poorly understood functions of MIM in cancer. Copyright © 2020 Sarapulov, Petrov, Hernández-Pérez, Šuštar, Kuokkanen, Cords, Samuel, Vainio, Fritzsche, Carrasco and Mattila.

Citation

Alexey V Sarapulov, Petar Petrov, Sara Hernández-Pérez, Vid Šuštar, Elina Kuokkanen, Lena Cords, Rufus V M Samuel, Marika Vainio, Marco Fritzsche, Yolanda R Carrasco, Pieta K Mattila. Missing-in-Metastasis/Metastasis Suppressor 1 Regulates B Cell Receptor Signaling, B Cell Metabolic Potential, and T Cell-Independent Immune Responses. Frontiers in immunology. 2020;11:599