Work

Acute ischaemic stroke alters the composition and function of circulating B cells

Year: 2025

Type: article

Abstract: • Acutely after stroke, circulating MZ-like B cells (an important source of early pathogen protective IgM) are substantially reduced in frequency, in comparison to non-stroke controls. • B cells show altered innate-like functionality, with reduced capacity to upregulate immunoglobulin M and cytokine production in response to bacterial-type (TLR9) stimulation. • MZ-like B cells are sensitive to noradrenaline signalling, and exposure of healthy B cells to noradrenaline ex vivo recapitulates cellular loss observed in stroke patients. • Lower MZ-like B cell frequencies are associated with stroke but not impacted by infection. Distinct B cell populations are found in circulation, including those with innate-like properties, that have varied functions in pathogen protection, vaccination and immunoregulation. The effects of tissue injury on circulating B cell populations are poorly explored. Here we show that, following acute ischaemic stroke (AIS), a common cause of neurological disability associated with systemic immune dysfunction, the circulating B cell compartment has altered functionality, alongside marked reductions in marginal zone (MZ)-like B cells, an innate-like B cell subset. Of note, release of Immunoglobulin (Ig) M, a key innate-like B cell-derived factor important in anti-bacterial responses, and regulatory cytokines including IL-6 and IL-10, was impaired upon stimulation of sorted B cells from AIS patients. B cells express adrenergic receptors, in both control and AIS patients, and release of the β2-AR agonist noradrenaline (NA) is elevated acutely following stroke. In vitro exposure of B cells from healthy individuals to NA recapitulated some of the functional modulation observed in AIS patients. Moreover, increased cell death of MZ-like B cells was observed in response to NA. Secondary infection is a common post-stroke complication that could be responsible for altered B cell characteristics. However, in line with the impact of NA on B cell populations, alterations were largely driven by stroke rather than secondary infection. Taken together, these findings demonstrate that neuroimmune factors are an important signal that could rapidly modify defined B cell populations early after tissue injury and highlight altered innate-like B cell function as a previously unappreciated characteristic of the systemic immunological response to acute stroke.

Source: Brain Behavior and Immunity

DOI: 10.1016/j.bbi.2025.106244