Lecture 14 - B cell effector function

• Types of mature B cells

  • Follicular B cells (FO)
  • Marginal Zone B cells (MZ)
• Follicular B cells (FO)


  • Recirculate in the body, secrete all classes of Ig, respond to T-dependent antigens
• Marginal Zone B cells (MZ)

  • Stay in the marginal zone of the spleen, secrete IgM, respond to T-independent antigens
• B cell class switching

  1. Weak tonic signals through BcRs activate Notch 2 signalling and push transitional cells to become MZ B cells

  2. Strong tonic signals through BcRs activate Bruton's tyrosine kinase (BTK) and prevent Notch 2 signals, pushing transitional cells to become FO B cells

  3. Somatic hypermutation enables the antigen-binding site to become more specific with each encounter with the same antigen
• Role of defined B cell isotypes in the immune response to infection

  • IgM
  • IgD
  • IgG
  • IgA
  • IgE
• IgM


  First antibody produced in a primary response, pentamer structure, low affinity for antigen
• IgD


  Co-expressed with IgM, function not clear but involved in defence of respiratory tract
• IgG


  Most abundant in serum, high affinity for antigens, crosses placenta to protect the fetus
• IgA


  Abundant in secretions, dimer structure, 4 antigen binding sites, monomeric form in serum
• IgE


  Lowest antibody in serum, triggers allergic reactions and asthma
• IgG and IgM antibodies


  Can bind to Fc-gamma receptors on phagocytes or NK cells to kill microbes
• Antibodies


  Can also activate complement to target microbes for phagocytes or directly kill the microbes
• Activation of Peripheral B cells

  1. B cell activation takes place in the secondary lymphoid tissues such as lymph nodes and spleen

  2. Activation is initiated at the junction of the B cell follicle and T cell zone

  3. B cells receiving activation signals enter specialised germinal centers within B cell follicles

  4. Co-receptors Ig-alpha Ig-beta have tyrosine kinase activity

  5. Complement bound to pathogen can bind complement receptor 2 (CR2/CD21)

  6. CR2/CD19/CD81 form a co-receptor complex that provides amplification of signals through the BcR

  7. CD4+ T cell help is vital for activation and differentiation of B cells into plasma cells
• Role of Germinal Centres

  1. Germinal centres are dynamic environments where B cells undergo clonal expansion, somatic hypermutation and class switching of Ig to the most appropriate class to deal with the microbe

  2. CD4+ Tfh (follilcular helper) cells are essential for germinal centre formation, class swtiching and differentiation of activated B cells into plasma cells

  3. IL-21 is a key cytokine for germinal centre formation

  4. Somatic hypermutation enables the antigen-binding site to become more specific with each encounter with the same antigen

  5. Fc-gamma receptor 2B(CD32) is a negative regulator of B cell activation
• Switching off B cells effector functions

  1. Diminished antigen and less T cell support enable de-activating Fc-gamma receptor 2B to be triggered

  2. Mutations in Fc-gamma receptor 2B are linked to several autoimmune conditions

  3. Licenced thymic B cells can delete autoreactive CD4+ T cells that are specific for the self-antigen the thymic B cell presented(AIRE dependent and non-AIRE dependent)

  4. Ectopic germinal centres in the thymus accurately predict the prognosis of autoimmune conditions such as Myasthenia Gravis

  5. Thymic B cells produce autoantibodies of IgG1 isotype, which binds to acetylcholine receptors and blocks their function

  6. IgG1 activates the complement cascade, resulting in nerve damage
• Location of Thymic B cells

  • Thymic B cells represent approx. 0.5-1% of all immune cells within the thymus
  • They are present from foetal age through to aged adult in both mice and humans
  • The numbers of thymic B cells increase with age
• Development of Thymic B cells

  1. Thymic B cells can originate from either peripheral B cells, from the bone marrow or intrathmyic sources

  2. They are involved in negative selection of autoreactive CD4+ T cells

  3. Peripheral B cells migrate to the thymus and express endogenous self antigens

  4. Thymic B cells interact with autoreactive CD4+ T cells that are specific for the self antigen the thymic B cell presents, both AIRE dependent and non-AIRE dependent
• Putative Function of Rogue Thymic B cells


  • They produce autoantibodies of IgG1 isotype that bind to acetylcholine receptors, blocking their function
  • IgG1 produced by thymic B cells activates the complement cascade, resulting in nerve damage
  • Abnormal ectopic germinal centres form in the thymus of Myasthenia Gravis patients and are predictive of disease progression
  • Thymic B cells play a role in the autoimmune pathology of Myasthenia Gravis disease subtypes, contributing to the production of autoantibodies that attack acetylcholine receptors
• T-dependent antigens require helper T cells to activate B cells through cytokines like IL-21.
• B cells can be activated by T-independent antigens, such as polysaccharides or lipopolysaccharide (LPS), which directly activate the BCR.