Hspa13 Promotes Plasma Cell Production and Antibody Secretion

B cell and plasma cell fates are controlled by different transcriptional networks, as exemplified by the mutually exclusive expression and cross-antagonism of the B cell identity factor Pax5 and the plasma cell regulator Blimp1. It has been postulated that repression of Pax5 by Blimp1 is essential for plasma cell development. Here, we challenged this hypothesis by analyzing the IghPax5/+ mouse, which expressed a Pax5 minigene from the immunoglobulin heavy-chain locus. Despite high Pax5 expression, plasma cells efficiently developed in young IghPax5/+ mice at steady state and upon immunization, while their number moderately declined in older mice. Although Pax5 significantly deregulated the plasma cell expression program, key plasma cell regulators were normally expressed in IghPax5/+ plasma cells. While IgM and IgA secretion by IghPax5/+ plasma cells was normal, IgG secretion was modestly decreased. Hence, Pax5 repression is not essential for robust plasma cell development and antibody secretion, although it is required for optimal IgG production and accumulation of long-lived plasma cells.

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Involvement of Twisted Gastrulation in T Cell-Independent Plasma Cell Production

The Journal of Immunology ◽

10.4049/jimmunol.1001833 ◽

2011 ◽

Vol 186 (12) ◽

pp. 6860-6870 ◽

Cited By ~ 10

Author(s):

Sotiris Tsalavos ◽

Katerina Segklia ◽

Ourania Passa ◽

Anna Petryk ◽

Michael B. O’Connor ◽

...

Keyword(s):

T Cell ◽

Plasma Cell ◽

Cell Production ◽

Twisted Gastrulation

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Analysis of long-lived plasma cell production and regulation: Implications for vaccine design for aquaculture

Aquaculture ◽

10.1016/j.aquaculture.2004.12.024 ◽

2005 ◽

Vol 246 (1-4) ◽

pp. 1-9 ◽

Cited By ~ 15

Author(s):

Stephen Kaattari ◽

Erin Bromage ◽

Ilsa Kaattari

Keyword(s):

Plasma Cell ◽

Vaccine Design ◽

Cell Production

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Plasma cell maintenance and antibody secretion are under the control of Sec22b-mediated regulation of organelle dynamics

10.1101/2022.01.14.476154 ◽

2022 ◽

Author(s):

Amelie Bonaud ◽

Laetitia Gargowitsch ◽

Simon Gilbert ◽

Elanchezhian Rajan ◽

Pablo Canales-Herrerias ◽

...

Keyword(s):

Plasma Cell ◽

Cell Biology ◽

Plasma Cells ◽

Critical Role ◽

Serum Antibody ◽

Cellular Mechanisms ◽

Antibody Titres ◽

And Function ◽

Antibody Secretion ◽

Cell Maintenance

Despite the essential role of plasma cells in health and disease, the cellular mechanisms controlling their survival and secretory capacity are still poorly understood. Here, we identified the SNARE Sec22b as a unique and critical regulator of plasma cell maintenance and function. In absence of Sec22b, plasma cells were barely detectable and serum antibody titres were dramatically reduced. Accordingly, Sec22b deficient mice fail to mount a protective immune response. At the mechanistic level, we demonstrated that Sec22b is indispensable for efficient antibody secretion but also for plasma cell fitness through the regulation of the morphology of the endoplasmic reticulum and mitochondria. Altogether, our results unveil a critical role for Sec22b-mediated regulation of plasma cell biology through the control of organelle dynamics.

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Active Inhibition of Plasma Cell Development in Resting B Cells by Microphthalmia-associated Transcription Factor

Journal of Experimental Medicine ◽

10.1084/jem.20040612 ◽

2004 ◽

Vol 200 (1) ◽

pp. 115-122 ◽

Cited By ~ 59

Author(s):

Ling Lin ◽

Andrea J. Gerth ◽

Stanford L. Peng

Keyword(s):

Transcription Factor ◽

B Cells ◽

B Cell ◽

Plasma Cell ◽

Cell Activation ◽

Terminal Differentiation ◽

B Cell Activation ◽

Autoantibody Production ◽

B Cell Homeostasis ◽

Antibody Secretion

B cell terminal differentiation involves development into an antibody-secreting plasma cell, reflecting the concerted activation of proplasma cell transcriptional regulators, such as Blimp-1, IRF-4, and Xbp-1. Here, we show that the microphthalmia-associated transcription factor (Mitf) is highly expressed in naive B cells, where it antagonizes the process of terminal differentiation through the repression of IRF-4. Defective Mitf activity results in spontaneous B cell activation, antibody secretion, and autoantibody production. Conversely, ectopic Mitf expression suppresses the expression of IRF-4, the plasma cell marker CD138, and antibody secretion. Thus, Mitf regulates B cell homeostasis by suppressing the antibody-secreting fate.

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