B cell Immunodeficiency

这是一篇关于B cell Immunodeficiency的思维导图，其内容包括X—linked agammaglobulinemia(XLA),Hyper Igm syndrome等四个方面的内容

B cell Immunodeficiency

• X-linked agammaglobulinemia (XLA)
  • Cause by a mutation in the gene coding for Btk.
  • Resulting in an inability of pre-B cells to make a complete BCR, leading pre-B cell apoptosis
  • Block B cell development which leads to a lack of antibody production
  • Disease detect after 6-9 mths
  • Susceptible to recurrent infection by progenitor bacteria (Pneumocci, Streptococci)
  • Treatment is routine intravenous Ig therapy
• Hyper IgM syndrome
  • Family of genetic disorder associated with an absence of Isotypes switching (No IgG, IgA)
  • Compensatory increased in IgM in serum
  • Patients have increased susceptibility to bacterial infection
  • Treatment
    • Routine intravenous Ig therapy
  • X-linked Hyper IgM syndrome
    • Caused by mutation in CD40
      • Defective CD40 signalling
        • Isotype switching
        • Affinity maturation
        • Memory B cell generation
        • Macrophage activation
    • CD40L on activated T cells
    • CD40 on APC (B cells, macrophages, DC)
  • Hyper IgM syndrome type 2 / AID deficiency
    • Autosomal recessive disorder
    • Mutation in activation-induced cytokine deaminase (AID)
      • AID initiates a cascade that result in dsDNA breaks
        • Allows new constant region in the heavy chain to be introduced
        • Point mutations in variable regions - somatic hypermutation
    • Results in a block in isotype switching and affinity maturation
    • Not as sever as X-linked hyper IgM syndrome
• Selective IgA immunodeficiency
  • Most common
  • Caused by a block in B cell differentiation into IgA-plasma cells
  • Increased susceptibility to respiratory infections (little or no IgA in mucosa)
• Common variable immunodeficiency (CVID)
  • Defect in 1 or more genes affecting B cell growth or stimulation
  • Present with variable reductions in IgG and IgA
  • Varying degrees of disease
  • Present later in life