Effect of Rituximab on B Cells
Rituximab causes rapid and sustained depletion of B cells by targeting the CD20 antigen on their surface, resulting in B cell lysis through multiple mechanisms including complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC). 1
Mechanism of Action
- Rituximab is a chimeric murine-human monoclonal antibody of the IgG1 subclass that specifically targets the CD20 antigen expressed on the surface of pre-B and mature B-lymphocytes 1
- Upon binding to CD20, rituximab mediates B-cell lysis through several mechanisms:
B Cell Depletion Timeline and Patterns
- Administration of rituximab results in rapid depletion of circulating and tissue-based B cells 1
- In NHL patients, CD19-positive B cells are depleted within the first three weeks of treatment with sustained depletion for up to 6-9 months post-treatment in 83% of patients 1
- In rheumatoid arthritis patients:
- The majority of patients demonstrate near-complete depletion (CD19 counts below the lower limit of quantification, 20 cells/μl) within 2 weeks after receiving the first dose 1
- Most patients show peripheral B-cell depletion for at least 6 months 1
- A small proportion (~4%) experience prolonged peripheral B-cell depletion lasting more than 3 years after a single course of treatment 1
Differential Effects on B Cell Subpopulations
- Rituximab has varying effects on different B cell subpopulations:
- More effective at depleting CD27- naïve B cells compared to CD27+ memory B cells 3
- IgD- B cells, including post-switched (IgD-CD27+) memory cells, show lower levels of rituximab internalization, potentially affecting depletion efficacy 4
- The drug can enrich B cells that undergo only one or two cell divisions and display an activated naïve phenotype (CD27-IgD+CD38-/+) 3
Effects on Immunoglobulin Levels
- Treatment with rituximab leads to reductions in serum immunoglobulin levels:
- In NHL patients, sustained and statistically significant reductions in both IgM and IgG serum levels are observed from 5 through 11 months following administration 1
- Approximately 14% of NHL patients have IgM and/or IgG serum levels below the normal range 1
- In RA patients, total serum immunoglobulin levels (IgM, IgG, and IgA) are reduced at 6 months, with the greatest change observed in IgM 1
B Cell Recovery
- B-cell recovery typically begins at approximately 6 months after treatment completion 1
- Median B-cell levels return to normal by 12 months following completion of treatment in NHL patients 1
- In granulomatosis with polyangiitis and microscopic polyangiitis patients:
Factors Affecting B Cell Depletion Efficacy
- Internalization of rituximab varies between patients and inversely correlates with cytotoxicity in whole blood B cell-depletion assays 4
- FcγRIIb (Fcγ receptor type IIb) regulates the internalization process of rituximab 4
- Anti-IgM stimulation can partially inhibit the internalization of rituximab 4
Clinical Implications
- The rapid and sustained B cell depletion makes rituximab effective in treating B-cell malignancies and autoimmune disorders 5, 6
- Variability in rituximab internalization correlates with impaired B cell depletion, potentially explaining differences in clinical response among patients 4
- Monitoring B cell phenotyping is useful to predict clinical relapses after rituximab treatment 6
Monitoring Response
- B cell phenotyping can help stratify patients according to response to treatment 6
- Recommended biomarkers to monitor by flow cytometry include:
Understanding the mechanism and patterns of B cell depletion with rituximab is crucial for optimizing treatment protocols and predicting clinical responses in various B cell-mediated diseases.