Blast from the Past…Memory B cells depleted by HSCT

Storek J, Zhao Z, Lin E, Berger T, McSweeney PA, Nash RA, Akatsuka Y, Metcalf MD, Lu H, Kalina T, Reindl M, Storb R, Hansen JA, Sullivan KM, Kraft GH, Furst DE, Maloney DG. Recovery from and consequences of severe iatrogenic lymphopenia (induced to treat autoimmune diseases).
Clin Immunol. 2004;113:285-98.

To ascertain the consequences of severe leukopenia and the tempo of recovery, we studied the immunity of 56 adult patients treated for multiple sclerosis or systemic sclerosis with autologous CD34 cell transplantation using extremely lymphoablative conditioning. NK cell, monocyte, and neutrophil counts recovered to normal by 1 month; dendritic cell and B cell counts by 6 months; and T cell counts by 2 years post-transplant, although CD4 T cell counts remained borderline low. Initial peripheral expansion was robust for CD8 T cells but only moderate for CD4 T cells. Subsequent thymopoiesis was slow, especially in older patients. Importantly, levels of antibodies, including autoantibodies, did not drop substantially. Infections were frequent during the first 6 months, when all immune cells were deficient, and surprisingly rare (0.21 per patient year) at 7-24 months pos-transplant, when only T cells (particularly CD4 T cells) were deficient. In conclusion, peripheral expansion of CD8 but not CD4 T cells is highly efficient. Prolonged CD4 lymphopenia is associated with relatively few infections, possibly due to antibodies produced by persisting pre-transplant plasma cells.

I didn’t have the MS HSCT data one our B cell paper, So thanks to Luis for finding this one. 

This is paper on HSCT, using cyclophosphamide and anti-Thymocyte globulin. Many people had MS. 

The repopulation kinetics are here.

What can you see?

Massive overshoot of B cells, due to mature B cell over population, that masks a major deletion of memory B cells. CD4 T cells disappear for over 2 years , CD8 are down for  8 months. Black bars 5th and 95th percentile of health and dotted line is the medium of health. No reports of autoimmunity in the report. Does this say anything, but the memory B cells were down

What does it look like?

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  • It looks like the immune system is unable to orchestrate inflammation, even if there is CNS damage going on. Which means that the absence of new lesions does not prove absence of MS activity.

    So, if you redefine relapse as a transient, clinically detectable neurological deficit caused by the pressure exerted on neurons by inflamed tissue (lesion), you witness an apparent absence of relapses too.

    • I once asked a HSCT Doc what was going on in the brains of these people, they said they didnt know, but I said the proceedure was killing people (about 2%) at the time, so the brains should tell a story, why were they not examined.

  • You have B and naive b cell repopulate like crazy,,, So Ebv is getting out of the system?
    Also Cd8 t cells have faster recover and thus also control any attempt
    of any infected ebv b cell to come up
    So this supports ebv ms Hypothesis

  • Could it be that those B cells need further follow up?
    Could be that this is allready telling us something about the immune system of ms patients?
    Meaning: imagine you do hsct in an healthy person or in a set of healthy persons do the B cell overshoot like that?
    Is this a feature exclusive of pwms or any auto immune disease?
    Thanks luis



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