V. Perfetti et al., AL AMYLOIDOSIS - CHARACTERIZATION OF AMYLOIDOGENIC CELLS BY ANTIIDIOTYPIC MONOCLONAL-ANTIBODIES, Laboratory investigation, 71(6), 1994, pp. 853-861
BACKGROUND: AL amyloidosis is characterized by systemic tissue deposit
ion of monoclonal Ig light chains synthesized by a bone marrow plasma
cell (PC) clone whose biologic characteristics remain undetermined. EX
PERIMENTAL DESIGN: Anti-idiotypic (anti-Id) monoclonal antibodies (MoA
bs) were used as specific probes to identify and study amyloidogenic c
ells in two patients by means of immnnofluorescence methods. These MoA
bs recognized populations of bone marrow pre-PC, PC, and peripheral bl
ood lymphocytes. To test whether the circulating Id+ lymphocytes were
capable of PC differentiation, peripheral blood lymphocytes were incub
ated with the differentiation-inducing agents, interleukin-3 and inter
leukin-6 in liquid culture. Preincubation with the anti-Id MoAb and co
mplement was used to inhibit formation of Id+PC in vitro. RESULTS: The
anti-Id MoAb identified three types of cells in the bone marrow with
cytoplasmic Ig having the same isotype as the monoclonal component: a)
lymphoid cells, that were slightly larger than common peripheral bloo
d lymphocytes (47% CD45RA+, 28% CD45R0+, 97% CD38-, 100% CD10-, 100% m
u-chain-); b) lymphoplasmacytoid cells with more abundant cytoplasm an
d Id+ Ig (CD45RA-, CD45RO-, CD10-, 53% CD38+); 3) mature PC that were
very similar to normal PC in morphology and antigenic profile (CD38+,
PCA1+, CD56-). A different picture was seen when anti-Id MoAb were use
d to detect peripheral blood Id+ elements: analysis revealed a populat
ion of mature resting surface Ig+ B lymphocytes. Circulating Id+ lymph
ocytes differentiated in vitro to PC and lymphoplasmacytoid cells that
were very similar to those present in the bone marrow. A significant
reduction in the number of Id+ PC was obtained after incubation with t
he anti-Id MoAb and complement. CONCLUSIONS: This study shows that the
amyloidogenic cell clone is constituted by at best the following cell
populations: a fraction of bone marrow cells (lymphoid, lymphoplasmac
ytoid cells and PC) and a subset of peripheral blood post-switched B l
ymphocytes. The results suggest a relationship among these cells, indi
cating that circulating Id+ lymphocytes may be the possible precursors
of the more differentiated bone marrow population.