BACKGROUND: AL amyloidosis is characterized by systemic tissue deposition of monoclonal Ig light chains synthesized by a bone marrow plasma cell (PC) clone whose biologic characteristics remain undetermined. EXPERIMENTAL DESIGN: Anti-idiotypic (anti-Id) monoclonal antibodies (MoAbs) were used as specific probes to identify and study amyloidogenic cells in two patients by means of immunofluorescence methods. These MoAbs recognized populations of bone marrow pre-PC, PC, and peripheral blood lymphocytes. To test whether the circulating Id+ lymphocytes were capable of PC differentiation, peripheral blood lymphocytes were incubated with the differentiation-inducing agents, interleukin-3 and interleukin-6 in liquid culture. Preincubation with the anti-Id MoAb and complement 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 blood lymphocytes (47% CD45RA+, 28% CD45R0+, 97% CD38-, 100% CD10-, 100% mu-chain-); b) lymphoplasmacytoid cells with more abundant cytoplasm and 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 used to detect peripheral blood Id+ elements: analysis revealed a population of mature resting surface Ig+ B lymphocytes. Circulating Id+ lymphocytes 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 the anti-Id MoAb and complement. CONCLUSIONS: This study shows that the amyloidogenic cell clone is constituted by at least the following cell populations: a fraction of bone marrow cells (lymphoid, lymphoplasmacytoid cells and PC) and a subset of peripheral blood post-switched B lymphocytes. The results suggest a relationship among these cells, indicating that circulating Id+ lymphocytes may be the possible precursors of the more differentiated bone marrow population.
BACKGROUND:AL amyloidosis is characterized by systemic tissue deposition of monoclonal Ig light chains synthesized by a bone marrow plasma cell (PC) clone whose biologic characteristics remain undetermined. EXPERIMENTAL DESIGN: Anti-idiotypic (anti-Id) monoclonal antibodies (MoAbs) were used as specific probes to identify and study amyloidogenic cells in two patients by means of immunofluorescence methods. These MoAbs recognized populations of bone marrow pre-PC, PC, and peripheral blood lymphocytes. To test whether the circulating Id+ lymphocytes were capable of PC differentiation, peripheral blood lymphocytes were incubated with the differentiation-inducing agents, interleukin-3 and interleukin-6 in liquid culture. Preincubation with the anti-Id MoAb and complement 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 blood lymphocytes (47% CD45RA+, 28% CD45R0+, 97% CD38-, 100% CD10-, 100% mu-chain-); b) lymphoplasmacytoid cells with more abundant cytoplasm and 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 used to detect peripheral blood Id+ elements: analysis revealed a population of mature resting surface Ig+ B lymphocytes. Circulating Id+ lymphocytes 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 the anti-Id MoAb and complement. CONCLUSIONS: This study shows that the amyloidogenic cell clone is constituted by at least the following cell populations: a fraction of bone marrow cells (lymphoid, lymphoplasmacytoid cells and PC) and a subset of peripheral blood post-switched B lymphocytes. The results suggest a relationship among these cells, indicating that circulating Id+ lymphocytes may be the possible precursors of the more differentiated bone marrow population.
Authors: Niels W C J van de Donk; Maarten L Janmaat; Tuna Mutis; Jeroen J Lammerts van Bueren; Tahamtan Ahmadi; A Kate Sasser; Henk M Lokhorst; Paul W H I Parren Journal: Immunol Rev Date: 2016-03 Impact factor: 12.988