B10 Cell Phenotypic Markers for Selective Immune Modulation

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Solution Overview

Problem

Current therapies for autoimmune and inflammatory diseases often target B cells non-specifically, leading to unintended consequences, and the role of regulatory B cell subsets in immune regulation remains unclear, particularly regarding their existence and function in humans.

Innovation Solution

Identification and characterization of a distinct B cell subset, B10 cells, which regulate T cell-mediated inflammatory responses through IL-10 secretion, allowing for targeted therapeutic manipulation of immune and inflammatory responses.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If B cells are depleted non-specifically using CD20 monoclonal antibody, then autoimmune and inflammatory diseases are treated, but pathogenic B cells cannot be distinguished from regulatory B cells leading to unintended consequences

Engineering Contradiction:
Improvetreatment effectivenessVSAvoidunintended consequences from non-specific depletion
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention segments the B cell population into distinct functional subsets: pathogenic B cells (CD1dlowCD5-) and regulatory B10 cells (CD1dhighCD5+). By identifying specific phenotypic markers, the patent enables selective targeting of pathogenic B cells while preserving regulatory B10 cells, thereby resolving the contradiction between effective disease treatment and avoidance of unintended consequences from non-specific depletion.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention applies local quality by assigning different functional properties to different B cell subsets based on their phenotypic characteristics. Regulatory B10 cells (CD1dhighCD5+) are identified as having immunosuppressive properties through IL-10 production, while pathogenic B cells (CD1dlowCD5-) are identified as disease-causing. This localized functional characterization enables selective therapeutic targeting.

Inventive Principle:
Principle #3Local quality

2Loss of information

If regulatory B cell subsets are not clearly defined, then the role of B cells in immunoregulation remains unclear, but therapeutic approaches cannot be specifically targeted

Engineering Contradiction:
Improveunderstanding of immune regulationVSAvoiddevelopment of targeted therapies
Core Design Contradiction:
Loss of informationVSEase of manufacture

Solution Approach 1:

The invention uses phenotypic markers as 'colors' to distinguish different B cell subsets. Regulatory B10 cells are identified by the specific phenotypic profile CD1dhighCD5+, while pathogenic B cells are identified as CD1dlowCD5-. These phenotypic 'color changes' or marker expressions enable clear definition of regulatory B cell subsets, providing the necessary information for both understanding immune regulation and developing targeted therapies.

Inventive Principle:
Principle #32Color changes

3Reliability

If B cell depletion is used to treat autoimmune diseases, then disease activity may be reduced, but B cell depletion may exacerbate certain conditions such as ulcerative colitis and psoriasis

Engineering Contradiction:
Improvedisease activity reductionVSAvoidexacerbation of certain conditions
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention extracts or removes only the pathogenic B cell subset (CD1dlowCD5-) from the B cell population, while leaving the regulatory B10 cells (CD1dhighCD5+) intact. This selective extraction approach treats autoimmune diseases by eliminating disease-causing cells without depleting protective regulatory cells, thereby avoiding the exacerbation of conditions like ulcerative colitis and psoriasis that occurs with non-specific B cell depletion.

Inventive Principle:
Principle #2Taking out (Extraction)

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

B10 cells can be used to treat autoimmune and inflammatory diseases by expanding their populations or inhibiting their function, providing a specific approach to modulate immune responses and improve disease outcomes.

Implementation Method 1

B10 cells, that regulate T cell mediated inflammatory responses through the secretion of interleukin-10 (IL-10)

Methodology Applied
Scientific EffectCytokine secretion:

Data Source

PatentUS10131875B2Regulatory B cells and their uses
Publication Date: 2018.11.20 DUKE UNIV
  • US10131875B2 patent drawing
  • US10131875B2 patent drawing
  • US10131875B2 patent drawing

AI summary

The present invention relates to a distinct B cell subset, B10 cells, that regulate T cell mediated inflammatory responses through the secretion of interleukin-10 (IL-10). The invention also relates to the use of B10 cells in the manipulation of immune and inflammatory responses, and in the treatment of disease. Therapeutic approaches involving adoptive transfer of B10 cells, or expansion of their endogenous levels for controlling autoimmune or inflammatory diseases and conditions are described. Ablation of B10 cells, or inhibition of their IL-10 production can be used to upregulate immunodeficient conditions, ameliorate infectious diseases and/or to treat tumors/cancer. Diagnostic applications are also encompassed.