Intruders or protectors - the multifaceted role of B cells in CNS disorders

Abstract

B lymphocytes are immune cells studied predominantly in the context of peripheral humoral immune responses against pathogens. Evidence has been accumulating in recent years on the diversity of immunomodulatory functions that B cells undertake, with particular relevance for pathologies of the central nervous system (CNS). This review summarizes current knowledge on B cell populations, localization, infiltration mechanisms, and function in the CNS and associated tissues. Acute and chronic neurodegenerative pathologies are examined in order to explore the complex, and sometimes conflicting, effects that B cells can have in each context, with implications for disease progression and treatment outcomes. Additional factors such as aging modulate the proportions and function of B cell subpopulations over time and are also discussed in the context of neuroinflammatory response and disease susceptibility. A better understanding of the multifactorial role of B cell populations in the CNS may ultimately lead to innovative therapeutic strategies for a variety of neurological conditions.

Keywords: B cells; brain injury; central nervous system; inflammation; neurodegenerative; neuroprotection.

FIGURE 1

B cell localization, functions, and therapeutic interactions in the CNS. (A) B cells that infiltrate into the CNS can originate in the local bone marrow of the calvarium, or from peripheral blood circulation. Lymphocytes can infiltrate into the CNS parenchyma through a damaged blood–brain barrier (BBB), the blood–cerebrospinal fluid barrier (BCSFB) of the choroid plexus (ChP) and circumventricular organs (CVOs), and the blood–meningeal barrier. (B) In the CNS, B cells can become activated via surface receptors, including BCRs and TLRs, and produce a variety of pro-inflammatory and anti-inflammatory cytokines that mediate complex immunomodulation in adjacent immune cells, particularly in T cells and myeloid populations. (C) Therapeutic strategies that are directly or indirectly mediated by B cells in the context of CNS disorders include B cell depletion strategies, modulatory drugs and biologics that alter the function of B cells, and direct application of B cells as an immunomodulatory cell-based therapeutic.

FIGURE 2

B cell subsets and their described functions in the CNS. Almost all major subsets of mature B cells have been described in the literature in connection with acute or chronic pathologies of the CNS. It is likely that future studies will further add to the growing list of B cell subsets and their complex roles in their interactions with the molecular microenvironment and specific cell subsets in the CNS. For illustration, surface markers typical of murine B cell subsets are shown.