From Marginal to Central: Marginal Zone-like B Cells as Critical Targets in Cladribine-Treated Multiple Sclerosis - Summary - MDSpire

Transitioning from Marginal to Central: The Role of Marginal Zone-like B Cells as Key Targets in Multiple Sclerosis Patients Treated with Cladribine

  • By

  • Marta Pirronello

  • Mario Picozza

  • Gisella Guerrera

  • Silvia Corbisiero

  • Andrea Misiti

  • Roberta C. Placido

  • Alice Verdiani

  • Lorenzo de Marco

  • Manolo Sambucci

  • Elena Olivieri

  • Daniela F. Angelini

  • Esmeralda Quartuccio

  • Luca Prosperini

  • Carla Tortorella

  • Maria C. Buscarinu

  • Valeria Zancan

  • Francesca de Masi

  • Marco Salvetti

  • Claudio Gasperini

  • Giovanna Borsellino

  • Luca Battistini

  • June 18, 2026

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Objective:

To investigate how cladribine modulates the composition and function of peripheral B-cell subsets in multiple sclerosis (MS) patients.

Approach:
  • B-cell Analysis: B-cell subset reconstitution dynamics were delineated over several years, profiling phenotypic features and proinflammatory capabilities.
Key Findings:
  • Marginal zone-like (MZ-like) memory B cells have a significant proinflammatory capacity in vitro.
  • MZ-like memory B cells are preferentially depleted and slow to reconstitute after cladribine treatment.
  • Double-negative (DN) B cells recover more rapidly despite exhibiting an activated phenotype.
Interpretation:

The findings suggest that alternative memory B cells, particularly the IgM-producing MZ-like subset, are key contributors to MS immunopathology and selective targets of cladribine.

Limitations:
  • The sample size was limited to 36 MS patients.
  • The study was conducted at specific hospitals, which may affect generalizability.
Conclusion:

Cladribine treatment preferentially targets MZ-like memory B cells, which may underpin its durable efficacy in MS.

Original Source(s)

From Marginal to Central: Marginal Zone-like B Cells as Critical Targets in Cladribine-Treated Multiple Sclerosis

  • by Marta Pirronello, Mario Picozza, Gisella Guerrera, Silvia Corbisiero, Andrea Misiti, Roberta C. Placido, Alice Verdiani, Lorenzo de Marco, Manolo Sambucci, Elena Olivieri, Daniela F. Angelini, Esmeralda Quartuccio, Luca Prosperini, Carla Tortorella, Maria C. Buscarinu, Valeria Zancan, Francesca de Masi, Marco Salvetti, Claudio Gasperini, Giovanna Borsellino, Luca Battistini

  • June 18, 2026

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