Schafflick D, Wolbert J, Heming M, Thomas C, Hartlehnert M, Börsch AL, Ricci A, Martín-Salamanca S, Li X, Lu IN, Pawlak M, Minnerup J, Strecker JK, Seidenbecher T, Meuth SG, Hidalgo A, Liesz A, Wiendl H, Meyer Zu Horste G. Single-cell profiling of CNS border compartment leukocytes reveals that B cells and their progenitors reside in non-diseased meninges. Nat Neurosci. 2021 Sep;24(9):1225-1234. Epub 2021 Jul 12 PubMed.

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  1. This is an interesting paper that adds to recent work demonstrating that tissue-resident B cell progenitors and mature B cells reside in the dura matter, and it highlights their potential homeostatic functions. Additionally, these data add support to the idea that dural immunity may be an important site in neuroinflammatory conditions, including autoimmune diseases (Rustenhoven et al., 2021). 

    Interestingly, the authors suggest that B cell recruitment from local bone marrow is not a major source of infiltration—rather, their maintenance occurs predominantly via dural precursors. Given that different studies (Cugurra et al., 2021; Brioschi et al., 2021) use different approaches to answer these questions, the exact contribution from each route remains to be clarified.

    References:

    Rustenhoven J, Drieu A, Mamuladze T, de Lima KA, Dykstra T, Wall M, Papadopoulos Z, Kanamori M, Salvador AF, Baker W, Lemieux M, Da Mesquita S, Cugurra A, Fitzpatrick J, Sviben S, Kossina R, Bayguinov P, Townsend RR, Zhang Q, Erdmann-Gilmore P, Smirnov I, Lopes MB, Herz J, Kipnis J. Functional characterization of the dural sinuses as a neuroimmune interface. Cell. 2021 Jan 18; PubMed.

    Cugurra A, Mamuladze T, Rustenhoven J, Dykstra T, Beroshvili G, Greenberg ZJ, Baker W, Papadopoulos Z, Drieu A, Blackburn S, Kanamori M, Brioschi S, Herz J, Schuettpelz LG, Colonna M, Smirnov I, Kipnis J. Skull and vertebral bone marrow are myeloid cell reservoirs for the meninges and CNS parenchyma. Science. 2021 Jun 3; PubMed.

    Brioschi S, Wang WL, Peng V, Wang M, Shchukina I, Greenberg ZJ, Bando JK, Jaeger N, Czepielewski RS, Swain A, Mogilenko DA, Beatty WL, Bayguinov P, Fitzpatrick JA, Schuettpelz LG, Fronick CC, Smirnov I, Kipnis J, Shapiro VS, Wu GF, Gilfillan S, Cella M, Artyomov MN, Kleinstein SH, Colonna M. Heterogeneity of meningeal B cells reveals a lymphopoietic niche at the CNS borders. Science. 2021 Jun 3; PubMed.

    View all comments by Justin Rustenhoven

  2. I wish to congratulate the authors for their exciting publication and valuable contribution. Meningeal B cells have been hiding in plain sight, and yet they have received little attention. I believe that our studies will pave the way for a fertile line of research for years to come. It is intriguing to think of the meninges as a nursery for developing immune cells, such as B cells and possibly others. I am also fascinated by B cell trafficking through the dura lymphatics. Future studies need to reveal the biological meaning of this unexpected finding.

    Meningeal B cells might use the dura lymphatics as an exit route from the CNS compartment. Alternatively, this trafficking could be a highly specialized behavior of meningeal B cells to transport CNS antigens towards the cervical lymph nodes. I am sure that time will provide us with some answers. In our recent work, we provided evidence of early B cells migrating from the calvaria to the dura through a network of skull vascular channels. Here, Schafflick et al. propose that B cells progenitors may seed the dura during development and be maintained there long-term. This is certainly an intriguing hypothesis that deserves further investigation.

    View all comments by Marco Colonna

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  1. More Evidence for Meningeal B Cells