Differential involvement of the transcription factor Blimp-1 in T cell-independent and -dependent B cell differentiation to plasma cells.
Along humoral immune responses, different stimuli drive the differentiation of B lymphocytes to Ig-secreting plasma cells in discrete microenvironments. The Blimp-1 transcription factor is up-regulated early during the transition of mature B cells to IgM-secreting plasma cells. In the present study, we have examined the requirement of Blimp-1 in plasma cell formation after both T cell-independent (LPS) and -dependent (CD40 + IL-4, Th cell lines) stimulation of spleen B cells. B lymphocyte-induced maturation protein (Blimp-1) was expressed early after in vitro LPS stimulation, mainly in a population of IgM+Syndecan+CD43+ preplasma cells. In contrast, the BSAP transcription factor expressed in mature B cells was down-regulated during the differentiation to plasma cells. Treatment of these cultures with Blimp-1-specific antisense phosphorothioate oligonucleotides suppressed both Blimp-1 protein levels and the emergence of IgM+Syndecan+ cells and plasma cells. However, T-B cell cocultures of spleen B cells from C3H/HeJ (H-2k) mice and syngeneic autoreactive SR.10 Th2 cells submitted to the anti-Blimp-1 therapy did not show any significant reduction in IgM- and IgG1-secreting plasma cell formation. Spleen B cells treated with anti-CD40 mAb + IL-4 differentiated to IgG1-secreting cells without significant transcription of the Blimp-1 gene; anti-Blimp-1 treatment subsequently did not have any effect in the later cultures. Altogether, these results suggest that Blimp-1 transcription factor specifically promotes T cell-independent B cell differentiation to plasma cells, probably at preplasma cell stages. In contrast, T cell-dependent plasma cell formation likely evolves through Blimp-1-independent pathways.
Centro Nacional de Biología Fundamental, Instituto de Salud Carlos III, Majadahonda, Spain.
P G
PG
Soro
P
P
Morales-A
J A
JA
Martínez-M
S
S
Morales-A
S G
SG
Copín
M A
MA
Marcos
M L
ML
Gaspar
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000921:Antibody-Producing Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015703:Antigens, CD; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D019013:CD40 Antigens / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D015847:Interleukin-4 / Q000494:pharmacology; D051917:Leukosialin; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D010950:Plasma Cells / Q000166:cytology*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011509:Proteoglycans / Q000096:biosynthesis; D012097:Repressor Proteins; D012795:Sialoglycoproteins / Q000096:biosynthesis; D013234:Stem Cells / Q000276:immunology / Q000378:metabolism; D053667:Syndecans; D013601:T-Lymphocytes / Q000502:physiology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D019013:CD40 Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D051917:Leukosialin; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; C513258:Prdm1 protein, mouse; D011509:Proteoglycans; D012097:Repressor Proteins; D012795:Sialoglycoproteins; C497863:Spn protein, mouse; D053667:Syndecans; D014157:Transcription Factors; D015847:Interleukin-4; D000074462:Positive Regulatory Domain I-Binding Factor 1