Immune memory after vaccination is largely dependent on the combination of antibody
production from long-lived plasma cells, and a supporting pool of antigen-primed memory B
cells. It has been observed that individuals with certain immunosuppressive conditions or
treatments have a weakened B cell memory, but the mechanisms behind remain elusive. The
aim of this thesis was to evaluate B cell immunity in healthy children, and how HIV-1
infection, antineoplastic therapy, and rheumatic disease and treatment can impact on various
features of B cell memory induction and maintenance.
In paper I, we explored the hyperactivation of B cells observed in patients carrying HIV-1
infection, and showed that it can be partly induced by ligation of soluble cleaved CD27 to
CD70 on the surface of memory B cells. In paper II, we aimed at comparing the
establishment of serum antibody titers and memory B cells after vaccination against measles
and rubella in healthy children. We found that the memory B cell pool remained stable also
early after vaccination, whereas the corresponding serum IgG titers decayed with time. In
contrast, both the serum IgG levels and frequency of blood memory B cells in healthy young
adults appeared stable. This implied that the antibody production and memory B cell
compartment are two separate entities with independent regulation, and that it takes longer
time to establish a stable pool of circulating antibodies. How these two parts of B cell
memory are affected by immunosuppressive disease and treatment was addressed in papers
III and IV. In paper III, we used a rhesus macaque model for high-dose Doxorubicin
treatment, and concluded that the established vaccine-induced memory B cell pool was
depleted, contrary to long-lived plasma cells and the resulting serum IgG titers. These
observations supported the finding of independent regulation of the two B cell memory
compartments, and revealed different sensitivity to chemotherapy. The bone marrow plasma
cell niche was additionally studied in an in vitro model for plasma cell – stromal cell cross
talk, where we discovered that in vivo relevant concentrations of Doxorubicin could hamper
the output of pivotal survival factors from stromal cells. In paper IV, we examined memory
B cells and circulating IgG titers in children with rheumatic disease, treated with low-dose
Methotrexate and TNF-α inhibition. We noted that serum IgG titers against tetanus were
lower in rheumatic patients than in healthy controls, and that patients who had only received
one measles vaccine dose had lower levels of measles-specific memory B cells. This stresses
the importance for children with rheumatic disease and treatment to follow the full vaccine
schedule.
To summarize, this thesis has contributed to enhanced knowledge on how B cell memory is
induced, preserved and at risk of disruption by common immune disorders and treatment.
Hopefully, our findings can aid future improvement of functional vaccine regimes for
immunocompromised children
