AL amyloidosis: Characterization of amyloidogenic cells by anti-idiotypic monoclonal antibodies

V. Perfetti, V. Bellotti, P. Garini, I. Zorzoli, B. Rovati, M. G. Marinone, G. Ippoliti, G. Merlini

Research output: Contribution to journalArticle

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Abstract

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% CD45RO+, 97% CD38-, 100% CD10-, 100% μ-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.

Original languageEnglish
Pages (from-to)853-861
Number of pages9
JournalLaboratory Investigation
Volume71
Issue number6
Publication statusPublished - 1994

Fingerprint

Amyloidosis
Plasma Cells
Anti-Idiotypic Antibodies
Monoclonal Antibodies
Lymphocytes
Bone Marrow Cells
Bone Marrow
Population
B-Lymphocytes
Clone Cells
Interleukin-3
Fluorescent Antibody Technique
Cell Differentiation
Interleukin-6
Cytoplasm
Light

Keywords

  • B lymphocytes
  • Plasma cell precursors

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

AL amyloidosis : Characterization of amyloidogenic cells by anti-idiotypic monoclonal antibodies. / Perfetti, V.; Bellotti, V.; Garini, P.; Zorzoli, I.; Rovati, B.; Marinone, M. G.; Ippoliti, G.; Merlini, G.

In: Laboratory Investigation, Vol. 71, No. 6, 1994, p. 853-861.

Research output: Contribution to journalArticle

Perfetti, V, Bellotti, V, Garini, P, Zorzoli, I, Rovati, B, Marinone, MG, Ippoliti, G & Merlini, G 1994, 'AL amyloidosis: Characterization of amyloidogenic cells by anti-idiotypic monoclonal antibodies', Laboratory Investigation, vol. 71, no. 6, pp. 853-861.
Perfetti, V. ; Bellotti, V. ; Garini, P. ; Zorzoli, I. ; Rovati, B. ; Marinone, M. G. ; Ippoliti, G. ; Merlini, G. / AL amyloidosis : Characterization of amyloidogenic cells by anti-idiotypic monoclonal antibodies. In: Laboratory Investigation. 1994 ; Vol. 71, No. 6. pp. 853-861.
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abstract = "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{\%} CD45RO+, 97{\%} CD38-, 100{\%} CD10-, 100{\%} μ-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.",
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T2 - Characterization of amyloidogenic cells by anti-idiotypic monoclonal antibodies

AU - Perfetti, V.

AU - Bellotti, V.

AU - Garini, P.

AU - Zorzoli, I.

AU - Rovati, B.

AU - Marinone, M. G.

AU - Ippoliti, G.

AU - Merlini, G.

PY - 1994

Y1 - 1994

N2 - 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% CD45RO+, 97% CD38-, 100% CD10-, 100% μ-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.

AB - 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% CD45RO+, 97% CD38-, 100% CD10-, 100% μ-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.

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