GITRL+ IgDlow B Cells for Autoimmune Control and Treg Expansion
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Solution Overview
Problem
Existing treatments for autoimmune and inflammatory diseases fail to identify a definitive B cell subset that effectively regulates disease severity through mechanisms other than IL-10, and B cell therapies may interfere with pathogen clearance.
Innovation Solution
Administering GITRL+ IgDlow B cells, potentially engineered to enhance GITRL expression and reduce IgD expression, to stimulate CD4+Foxp3+ T regulatory cell proliferation, thereby treating autoimmune and inflammatory conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If B cell depletion therapy is used to treat autoimmune diseases, then disease severity is reduced, but pathogen clearance capacity is compromised
Solution Approach 1:
The patent segments the B cell population into distinct subsets based on IgD expression levels (IgDhigh versus IgDlow). By targeting only IgDhigh B cells for depletion while preserving IgDlow B cells, the therapy achieves disease control without compromising protective B cell functions such as pathogen clearance and Treg maintenance.
Solution Approach 2:
The patent applies local quality by creating a heterogeneous treatment outcome where different B cell subsets experience different fates. IgDhigh B cells are depleted to reduce autoimmunity, while IgDlow B cells are preserved to maintain immune protection and regulatory functions. This localized differential treatment resolves the contradiction between reducing disease severity and maintaining reliability.
2Reliability
If IL-10 producing B cells are targeted for therapy, then regulatory function is enhanced, but other protective B cell mechanisms are lost
Solution Approach 1:
The patent segments B cells into regulatory (IgDlow) and other protective subsets (IgDhigh). By preserving IgDlow B cells that produce IL-10 and regulate Tregs, while depleting IgDhigh B cells, the therapy enhances regulatory function without losing other protective mechanisms provided by remaining B cell subsets.
Solution Approach 2:
The patent uses IgD expression level as an intermediary marker to identify and preserve regulatory B cells. This intermediary characteristic allows selective maintenance of IL-10 producing B cells that mediate Treg homeostasis, while eliminating other B cell subsets that provide diverse protective functions against pathogens.
3Object-affected harmful factors
If all B cell subsets are depleted to treat autoimmunity, then inflammation is reduced, but immune tolerance maintenance is compromised
Solution Approach 1:
The patent segments the B cell population to distinguish between inflammatory subsets (IgDhigh) and tolerance-maintaining subsets (IgDlow). Selective depletion of IgDhigh B cells reduces inflammation, while preservation of IgDlow B cells maintains immune tolerance through Treg homeostasis, resolving the contradiction between inflammation reduction and tolerance maintenance.
Solution Approach 2:
The patent applies local quality by creating differential outcomes for different B cell subsets. IgDhigh B cells are targeted for depletion to reduce inflammatory responses, while IgDlow B cells are preserved to maintain local immune tolerance mechanisms. This localized selective depletion resolves the contradiction between reducing harmful inflammation and maintaining protective tolerance.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The GITRL+ IgDlow B cells promote T regulatory cell expansion, effectively reducing autoimmune disease severity and inflammation, while maintaining immune system functionality.
Implementation Method 1
B cells have the ability to homeostatically expand Treg was glucocorticoid-induced tumor necrosis factor receptor (TNFR) ligand (GITRL)-dependent
Data Source
AI summary
GITRL+ IgDlow/â B cells as well as methods of making and using said cells are described herein. Also described are methods for treating an autoimmune disease or an inflammatory condition in a subject in need thereof of using said B cells. The B cells may be GITRL+ IgDlowCCR7+ CXCR5+ B cells or GITRL+ IgDlow CCR7+ CXCR5+ CD23+ CD24+ B cells.