What is a switched B cell?

Switched B Cells: Definition and Clinical Significance

A switched B cell is a mature B lymphocyte that has undergone class switch recombination, changing from expressing IgM/IgD to expressing IgG, IgA, or IgE antibodies while maintaining the same antigen specificity. 1

Characteristics of Switched B Cells

Switched B cells are characterized by:

• CD27+IgM-IgD- phenotype (class-switched memory B cells) 1, 2
• Loss of surface IgM and IgD expression
• Expression of secondary immunoglobulin isotypes (IgG, IgA, or IgE)
• Retention of the same antigen-binding variable region
• Enhanced effector functions compared to naive or unswitched B cells

Mechanism of Class Switching

Class switch recombination (CSR) is the molecular process that generates switched B cells:

• Occurs in germinal centers of secondary lymphoid tissues
• Requires activation-induced cytidine deaminase (AID) enzyme 3
• Involves DNA recombination that exchanges the constant region gene segments
• Preserves the variable region (maintaining antigen specificity)
• Directed by specific cytokines that determine which isotype is produced 4
• Requires CD40-CD40L interaction between B cells and T helper cells 1

Clinical Significance

Switched B cells have significant clinical importance:

• Diagnostic value: Reduced numbers of class-switched memory B cells (CD27+IgM-IgD-) are seen in:

  • Common Variable Immunodeficiency (CVID) 1
  • Hyper IgM syndrome (particularly CD40L and CD40 deficiencies) 1, 5
  • Activation-induced cytidine deaminase (AID) deficiency 1
  • Uracil nucleoside glycosylase (UNG) deficiency 1

• Disease associations:

  • Decreased switched memory B cells correlate with increased risk of:
    • Granulomatous disease 1
    • Splenomegaly 1
    • Autoimmunity 6
    • Recurrent infections, particularly respiratory tract infections 1

• Therapeutic implications:

  • Patients with defects in class switching often require immunoglobulin replacement therapy 1, 5
  • Monitoring switched B cell populations can help guide treatment decisions in immunodeficiencies 1

Immunological Classification

In modern B cell classification schemes, switched B cells are identified as:

• Part of the memory B cell compartment
• Distinguished from naive B cells and unswitched memory B cells
• Identifiable by flow cytometry using markers including CD27, IgD, IgM, and CD19 2
• Further subdivided based on additional markers like CD39 and CD11c that indicate specialized functions 2

Clinical Pitfalls and Considerations

• Age-dependent reference ranges must be used when interpreting switched memory B cell counts, as these populations are developmentally regulated 1
• Certain medications can affect class switching and memory B cell populations (anticonvulsants, immunosuppressants) 1
• Switched memory B cells are particularly important for protection against encapsulated bacteria and respiratory pathogens
• Defects in class switching may present with normal total B cell counts but abnormal memory B cell subpopulations 1

Understanding switched B cells is crucial for diagnosing and managing primary immunodeficiencies, particularly those affecting antibody production and class switching mechanisms.