Early generated B-1–derived B cells have the capacity to progress to become mantle cell lymphoma–like neoplasia in aged mice

Kyoko Hayakawa, Anthony M. Formica, Yuka Nakao, Daijyu Ichikawa, Susan A. Shinton, Joni Brill-Dashoff, Mitchell R. Smith, Herbert C. Morse, Richard R. Hardy

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

In mice, fetal/neonatal B-1 cell development generates murine CD5+ B cells (B1a) with autoreactivity. We analyzed B1a cells at the neonatal stage in a VH11/D/JH knock-in mouse line (VH11t) that generates an autoreactive antiphosphatidylcholine BCR. Our study revealed that antiphosphatidylcholine B1a cells develop in liver, mature in spleen, and distribute in intestine/colon, mesenteric lymph node (mLN), and body cavity as the outcome of B-1 cell development before B-2 cell development. Throughout life, self-renewing B-1 B1a cells circulate through intestine, mesenteric vessel, and blood. The body cavity–deposited B1a cells also remigrate. In old age, some B1a cells proceed to monoclonal B cell lymphocytosis. When neonatal B-1 B1a cells express an antithymocyte/Thy-1 autoreactivity (ATA) BCR transgene in the C.B17 mouse background, ATA B cells increase in PBL and strongly develop lymphomas in aging mice that feature splenomegaly and mLN hyperplasia with heightened expression of CD11b, IL-10, and activated Stat3. At the adult stage, ATA B cells were normally present in the mantle zone area, including in intestine. Furthermore, frequent association with mLN hyperplasia suggests the influence by intestinal microenvironment on lymphoma development. When cyclin D1 was overexpressed by the Em-cyclin D1 transgene, ATA B cells progressed to further diffused lymphoma in aged mice, including in various lymph nodes with accumulation of IgMhiIgDloCD5+CD232CD43+ cells, resembling aggressive human mantle cell lymphoma. Thus, our findings reveal that early generated B cells, as an outcome of B-1 cell development, can progress to become lymphocytosis, lymphoma, and mantle cell lymphoma–like neoplasia in aged mice.

Original languageEnglish
Pages (from-to)804-813
Number of pages10
JournalJournal of Immunology
Volume201
Issue number2
DOIs
Publication statusPublished - 2018 Jul 15

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B-Lymphocytes
Neoplasms
Lymph Nodes
Intestines
Mantle-Cell Lymphoma
Lymphocytosis
Lymphoma
Cyclin D1
Transgenes
Hyperplasia
Splenomegaly
Interleukin-10
Blood Vessels
Colon
Spleen
Liver

ASJC Scopus subject areas

  • Immunology

Cite this

Early generated B-1–derived B cells have the capacity to progress to become mantle cell lymphoma–like neoplasia in aged mice. / Hayakawa, Kyoko; Formica, Anthony M.; Nakao, Yuka; Ichikawa, Daijyu; Shinton, Susan A.; Brill-Dashoff, Joni; Smith, Mitchell R.; Morse, Herbert C.; Hardy, Richard R.

In: Journal of Immunology, Vol. 201, No. 2, 15.07.2018, p. 804-813.

Research output: Contribution to journalArticle

Hayakawa, K, Formica, AM, Nakao, Y, Ichikawa, D, Shinton, SA, Brill-Dashoff, J, Smith, MR, Morse, HC & Hardy, RR 2018, 'Early generated B-1–derived B cells have the capacity to progress to become mantle cell lymphoma–like neoplasia in aged mice', Journal of Immunology, vol. 201, no. 2, pp. 804-813. https://doi.org/10.4049/jimmunol.1800400
Hayakawa, Kyoko ; Formica, Anthony M. ; Nakao, Yuka ; Ichikawa, Daijyu ; Shinton, Susan A. ; Brill-Dashoff, Joni ; Smith, Mitchell R. ; Morse, Herbert C. ; Hardy, Richard R. / Early generated B-1–derived B cells have the capacity to progress to become mantle cell lymphoma–like neoplasia in aged mice. In: Journal of Immunology. 2018 ; Vol. 201, No. 2. pp. 804-813.
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AU - Ichikawa, Daijyu

AU - Shinton, Susan A.

AU - Brill-Dashoff, Joni

AU - Smith, Mitchell R.

AU - Morse, Herbert C.

AU - Hardy, Richard R.

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