chaperoning DNA mismatch repair enzymes to the V region

converting C to G in single stranded DNA

converting C to U in single stranded DNA

transcription of the V region to make DNA single stranded

Because IgM is a pentamer with 10 antigen-binding sites, IgM secreted antibodies can have the same binding strength as secreted IgG despite being lower affinity

Because the same enzyme initiates CSR and somatic hypermutation (SHM), CSR and affinity maturation always occur together

IgM antibodies by definition differ in affinity to IgG antibodies 

Simultaneous production of IgM and IgG is central to affinity maturation

there is a slow increase in serum antibody before reaching a plateau

antibody in the serum declines slowly and then plateaus

antibody in the serum plateaus and then declines rapidly

antibody in the serum plateaus and remains at this level, usually for decades

Loss of regulatory T cells (Tregs) is associated with the onset of SLE

Lupus (SLE) is an autoimmune disease that targets a single organ

Auto-reactive B-cell activation is sufficient to cause autoimmune diseases

Inflammation is a necessary trigger for most autoimmune diseases

To bring Rituxmab into line with all other therapeutic monoclonal antibodies for dosage and treatment frequency.

To prolong the half-life of the antibody in the patients, thereby improving its efficacy.

To avoid an immune response in the recipients.

To activate immune functions of the patient.

We need to use non-targeting drugs so that broader immune pathways can be regulated

We need to give multiple drugs all at once to maximise the treatment effect

We need to invent one drug for all autoimmune diseases

We need to align with a treatment algorithm for autoimmune diseases in case one drug has insufficient response

Autoantibodies target red blood cells and cause red blood cell lysis

Autoantibodies target the thyroid-stimulating hormone receptor

Autoantibodies block Anti-N-methyl-d-aspartate-receptor (NMDAR) in CNS

Autoantibodies form immune complexes in the kidney, which recruits inflammatory cells

Autoreactive B cells form ectopic lymphoid structures in tissues by forming immune complexes with other immune cells

Autoreactive B cells present antigens to antigen presenting cells to stimulate T cells

Autoantibodies derived from autoreactive B cells recognise self-antigens and form immune-complex deposition in organs triggering inflammation

Autoreactive B cells produce granzyme to destroy own tissues

A breakdown in central tolerance in the bone marrow allowing self-reactive lymphocytes to develop

A genetic predisposition that is triggered by environmental agents

Infection with a pathogen that expresses antigens that mimic a self-antigen

A mutation affecting tolerance in the thymus or in Treg development

Polymorphisms in both innate and adaptive immune cells may cause the disease

Anifrolumab targeting B cells has been proven to be effective in treating SLE 

It is caused by autoantibodies directed against erythrocytes

It is caused by autoantibodies directed against hepatocytes