Hm. Ogmundsdottir et al., Enhanced B cell survival in familial macroglobulinaemia is associated withincreased expression of Bcl-2, CLIN EXP IM, 117(2), 1999, pp. 252-260
A family with three cases of macroglobulinaemia of undetermined significanc
e (MGUS), and one case each of immunoblastic lymphoma, Waldentrom's macrogl
obulinaemia and multiple myeloma was first described 20 years ago. We have
previously identified 10 out of 35 healthy family members tested whose lymp
hocytes produced abnormally high amounts of immunoglobulins in culture. In
the present study lymphocyte subpopulations of these hyper-responders have
been further characterized and lymphocyte reactivity and survival in vitro,
have been studied. No differences were detected in the proportions of rest
ing B lymphocytes (CD19(+)) co-expressing CD5, CD10, CD11b, or CD38, and th
e CD4/CD8 ratio of T cells was normal before and after stimulation with pok
eweed mitogen (PWM). The initial rate of response in terms of immunoglobuli
n production was not increased, but immunoglobulin levels continued to rise
during the second week of culture whereas the production peaked at 8 days
in control cultures. This was associated with significantly greater surviva
l of lymphocytes and at 14 days surviving B cells could only be identified
in samples from hyper-responders. A lymph node removed because of tuberculo
sis from a family member 23 years before the diagnosis of multiple myeloma
showed very marked Bcl-2 expression in a B cell follicle. This was not seen
in a tuberculous lymph node from an unrelated subject. Stimulated cultures
from three hyper-responders tested demonstrated significantly higher reten
tion of Bcl-2 in B cells compared with one family control and six unrelated
controls. We conclude that the increased production of immunoglobulins pre
viously observed in this family with an inherited tendency for benign and m
alignant B cell proliferation is the result of enhanced B cell survival, wh
ich is associated with increased expression of Bcl-2 following stimulation.