Altered Functional B Cell Subsets
Bansal moved on to discussing
his own recent study. Most of his patients were classed as moderate, two were severe. All fulfilled the CCC. All were negative for routine antibodies and none had gluten sensitivity. All were seen at the same time of day; all were assessed in serum for a wide range of exotic antibodies seen in neurological problems: all those tests were negative.
But when they studied B-cell gating, what they found was that levels of
transitional B cells were increased in CFS.
B cells are produced in the bone marrow, and migrate via secondary lymphoid tissues (such as the spleen and the lymph nodes) where they are called transitional B cells, some of which differentiate into mature B lymphocytes. Bansal thinks what may be happening is that some problem in the transition of these cells means that they haven’t been through the same ‘checkpoints’ as normal B cells, meaning that the B cells in CFS patients are more likely to produce low
avidity antibodies – antibodies which bind weakly with the antigens they are supposed to attack, perhaps because some of their antigen-binding sites are not functioning properly.
[Interestingly, this hypothesis may connect somehow with the
recently-discovered mechanism of Rituximab reported in Cancer last month: Rituximab binds to one side of a diseased B-cell and dramatically increases the success rate of NK cells in destroying the diseased cell. Could Rituximab be assisting somehow with the faulty binding of these low avidity antibodies?]
Bansal also finds that naïve B cells are a higher percentage of all B cells in the CFS patients he studied – these are the cells that haven’t undergone the ‘checkpoints’. He noted that other results show lowered levels of IL 21,12, and 27 – all of which are involved in the correct maturation of B cells. So it would make sense to him that the B cells aren’t undergoing the correct checkpoint analysis. But then looking at T cells, a number of abnormalities have been reported. The end result: an abnormal interaction between T and B cells, and the B cells are not regulated properly. As the interaction proceeds, Bansal warned, these responses will mature, the avidity gets higher, and the process becomes harder to reverse, which would make early diagnosis particularly important.
Summarising his findings, Bansel re-iterated that he believes he is seeing impaired maturation of B cells, less anti-viral cytokines and especially less of those involved in B cell regulation, resulting in impaired T-Lymphocyte homing receptors.
Conclusions
Bansal therefore proposes that the initial problem in CFS may involve B cell dysregulation, perhaps after a series of viral infections, and especially if the patient is under stress as well at the time of infection. In some people, the B cells then start to make auto-antibodies against neural receptors in the CNS and the periphery. These auto-antibodies contribute to worsened arousal mechanisms, causing sleep dysregulation and autonomic dysfunction. Some may also target mitochondrial proteins and produce delayed PEM.
In perhaps one of the most important take-home messages of the day, Bansal suggested that while removing these auto-antibodies has been found to reduce symptoms, for a lasting response it may also be necessary to suppress the action of certain viruses which encourage the survival of auto-reactive B cells. So we may not only need to ‘reboot’ the B cells; we may also need to get rid of those viruses as well.
In summary: it’s a very complex disease, he said, but he believes we are now entering a ‘paradigm shift’. In Bansal’s opinion, it is very likely there is a subtle autoimmune phenomenon here, with antibodies targeting CNS proteins.
UK members know as much about immune and secondary infection evidence as I do. They also know a lot more about the political situation with ME/CFS in the UK. So, I'll leave it to the UK contingent to bring up the issues if they think they're relevant.
