Aberrations in peripheral B lymphocytes and B lymphocyte subsets levels in Parkinson disease: a systematic review

Abstract

Objective: The association of B lymphocytes and B lymphocyte subsets and Parkinson's disease (PD) is increasingly acknowledged. However, there is inconsistence in the alterations of B lymphocytes or B lymphocyte subsets in peripheral blood of PD patients. To comprehensively understand its changes in PD patients,it is necessary to conduct a systematic review on this subject.

Methods: PubMed, Cochrane Library, and MEDLINE databases were searched until 3^rd February 2024.

Results: We included 20 studies (n=2658) to conduct this systematic review. We conducted a qualitative analysis to assess the alterations of B lymphocytes and B lymphocyte subsets in the peripheral blood of individuals with PD. And studies reviewed demonstrated a significant decrease in the number of B cells, as well as immune dysregulation in the B lymphocyte subsets of these patients' peripheral blood.

Conclusion: Studies reviewed demonstrated that PD is linked to abnormalities in B lymphocytes and/or B lymphocytes subsets in peripheral blood. This study provides a novel perspective into the pathogenesis of PD, and future investigations into the B lymphocytes and/or B lymphocyte subsets as biomarkers and therapeutic targets for PD is warranted.

Keywords: B lymphocyte; B lymphocyte subsets; Immunity; Inflammation; Parkinson’s disease; Pathogenesis.

Figure 1

PRISMA flow diagram for study selection.

Figure 2

Potential roles for B cells in PD. The possible reasons for the decrease in B cells, the potential involvement of B cells in PD, and the diverse developmental stages of B cell subsets. B cell levels are reduced in PD patients for several possible reasons, including alpha-synuclein pathology, PD effect, age, clinical severity(H&Y), disease progresses, disease duration, the migration of B lymphocytes to other compartments, gender, medication use, and migration to secondary lymphoid organs. But B cells are activated and there is a significant increase in the pro-inflammatory cytokines TNF-α, IL-6 and GM-CSF, and a significant decrease in the anti-inflammatory cytokine IL-10 in PD, which eventually leads to deregulated neuroinflammation and subsequent dopaminergic neurodegeneration. IgG antibodies deposit on dopaminergic neurons in PD patients, and the Lewy bodies are also coated by IgG. Although anti-alpha-synuclein antibodies are present in the blood of PD patients, but it is still unclear whether these antibodies are the same as those that bind to neurons in the substantia nigra and Lewy bodies in these individuals. B cells are activated and the antigen presentation capacity of B cells is enhanced in PD patients. B lymphocytes can uptake, process, and present antigens to T cells, activating the immune response of T cells. T cell immune response can trigger type 1 pro-inflammatory activities and suppress type 2 anti-inflammatory activities, eventually resulting in deregulated neuroinflammation and subsequent dopaminergic neurodegeneration. T, T cell; USM B cells, un-class-switched memory B cells; CSM B cells, Class-switched Memory B cells; DNM B cells, Double Negative Memory B cells.