Fig. 5.

Potential pathogenic mechanisms of neuronal surface antibodies and B cell lineages underlying generation of antibody-secreting cells. a Antibodies against neuronal surface epitopes can mediate pathogenic effects through multiple mechanisms which include cross-linking and internalisation of the target, fixation of C1q and activation of the classical complement pathway, and direct interference with channel function including pharmacological-type block. b B cells are formed from haematopoietic stem cells in the bone marrow and undergo recombination of V, D and J immunoglobulin genes to generate a functional B cell receptor. They enter peripheral blood becoming a naïve B cell, and in lymphatic tissue encounter cognate antigen, leading to B cell activation and generation of germinal centres. In germinal centres, B cells process antigen and present it as peptide on surface MHC molecules to T-helper cells, which in turn provide support for the activated B cells. During the process of affinity maturation, B cells undergo somatic hypermutation leading to a diversity of antigen-specific B cell receptors. Alongside this, the immunoglobulin class often switches from IgM to IgG. This reaction generates memory B cells, as well as antibody-secreting cells in the periphery (plasmablasts). Antibody-secreting cells vary in their longevity and migration back to the bone marrow to a survival niche and are associated with long-term antibody secretion. Reproduced with permission from [102]