B and T cell activation for immune response

[microbio_geek15]

So, I know that B cells need T cell help for proper activation and isotope class switching. But, in some autoimmune diseases (such as Rheumatoid arthritis) antibodies are produced of the IgG isotope that are specific for DNA. DNA cannot be presented to MHCs on B cells, therefore it cannot be presented to T cells either. So how exactly would you get an auto immune response? Anyone have any ideas to explaining this phenomena?

 

Any help/insight would be much appreciated

[Xalatan]

This is how I understand autoimmune diseases and relevant pathophysiology that you have mentioned:

 

1. Anti-dsDNA antibody is pathognomonic of systemic lupus erythematosus, not rheumatoid arthritis. Rheumatoid factor is classically described as an anti-IgG IgM autoantibody.

2. Both SLE and RA are type 3 hypersensitivities, which means the underlying pathology involves immune complexes. Ie. Circulating pre-existent antibodies binding to the relevant antigens (dsDNA in the case of SLE, IgG in the case of RA), triggering immune-complex deposition and inflammation in areas of high vascular resistance, such as serosa, glomeruli, small vessels.

3. The pathophysiology you are describing involving B cells, antigen presentation, class switching and plasma cell production of auto-antibodies is defined as class 2 hypersensitivity. More classical examples of type 2 hypersensitivities include ABO incompatibility, Myasthenia gravis etc, not SLE and RA.

4. To directly answer your question on an immunological level, while it is true that antigens presented on MHC II molecules are peptides, B cells can actually undergo T-cell independent activation without the need for MHC II presentation. This is how IgM is produced as part of the innate first response without the need for isotope switching and IgG production. B cells can use their BCR to bind to PAMPs or DAMPs like foreign polysaccharide or DNA; the second signal is from macrophages rather than T cells, or in the case of a large bacterial antigen, extensive cross-linking to repetitive bacterial epitopes can also trigger the second signal in the B cell.