&lt;em&gt;In Vitro&lt;/em&gt; Generation of Murine Plasmacytoid Dendritic Cells from Common Lymphoid Progenitors using the AC-6 Feeder System

Chang, Shiun; Pai, Li‐Mei; Lee, Chien‐Kuo

doi:10.3791/53211

Cited by 2 publications

(2 citation statements)

References 24 publications

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“…Our findings raise the question of why B cell deficient muMT mice exhibit increased pDC frequencies, which compensate for B cell deficiency and permit antitumor immunity. pDCs and B cells share a common lymphoid progenitor (12,13). The genetic abnormality that makes the progenitor unable to differentiate into B cells in this model may permit differentiation into pDCs instead.…”

Section: Discussionmentioning

confidence: 98%

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Redefining innate natural antibodies as important contributors to anti-tumor immunity

Rawat

Tewari

Morrisson

et al. 2021

eLife

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Myeloid, T and NK cells are key players in the elimination phase of cancer immunoediting, also referred to as cancer immunosurveillance. However, the role of B cells and NAbs, which are present prior to the encounter with cognate antigens, has been overlooked. One reason is due to the popular use of a single B cell-deficient mouse model, muMT mice. Cancer models using muMT mice display a similar tumor burden as their WT counterparts. Empirically, we observe what others have previously reported with muMT mice. However, using two other B cell-deficient mouse models (IgHELMD4 and CD19creDTA), we show a 3 to 5-fold increase in tumor burden relative to WT mice. In addition, using an unconventional, non-cancer-related, immune neoantigen model where hypoxic conditions and cell clustering are absent, we provide evidence that B cells and their innate, natural antibodies (NAbs) are critical for the detection and elimination of neoantigen-expressing cells. Finally, we find that muMT mice display anti-tumor immunity because of an unexpected compensatory mechanism consisting of significantly enhanced Type 1 interferon (IFN)-producing plasmacytoid dendritic cells (pDCs), which recruit a substantial number of NK cells to the tumor microenvironment compared to WT mice. Diminishing this compensatory pDC-IFN-NK cell mechanism revealed that muMT mice develop a 3 to 5-fold increase in tumor burden compared to WT mice. In summary, our findings suggest that NAbs are part of an early defense against not only microorganisms and dying cells, but precancerous cells as well.

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Section: Discussionmentioning

confidence: 98%

“…We did not observe any substantial difference in mononuclear phagocyte populations between muMT and WT mice (data not shown). However, the numbers of pDCs, which are lymphoid in origin (12)(13)(14)(15), were significantly greater in the muMT mice compared to WT mice (Fig. 2A).…”

Section: Mumt Mice Have Excess Pdcs With Most Located In the Absentee B Cell Zonementioning

confidence: 95%

Redefining innate natural antibodies as important contributors to anti-tumor immunity

Rawat

Tewari

Morrisson

et al. 2021

eLife

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A critical role for B cells in cancer immune surveillance

Rawat

Tewari

Jakubzick

2020

Preprint

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It is commonly believed that B cells play no role in cancer immune surveillance. However, this conclusion is based on studies using only a single B cell-deficient mouse strain, muMT mice, which does not show increased tumorigenesis compared with wild-type (WT) mice. In this study, we demonstrate a critical role for B cells in anti-tumor immunity and identify the cellular mechanisms that make muMT mice a special case. First, we replicate previous findings using a melanoma model in muMT mice. Then, we show that in muMT mice, B-cell deficiency is compensated for by a significant increase in another potent anti-tumor cell type, Type-1 interferon (IFN I)-producing plasmacytoid DCs (pDCs), resulting in normative anti-tumor responses. Depleting pDCs in muMT mice resulted in a significant increase in tumor size and burden. Conversely, adoptive transfer of antibodies from naive WT serum into pDC-depleted muMT mice significantly decreased the tumor load to WT levels. Additionally, a B cell antibody repertoire-deficient mouse strain, IghelMD4 mice, showed a 3-fold increase in tumors relative to WT mice. Overall, these findings indicate the need for a diverse antibody repertoire for early neoplastic cell recognition and the critical role B cells play in anti-cancer immunity.

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<em>In Vitro</em> Generation of Murine Plasmacytoid Dendritic Cells from Common Lymphoid Progenitors using the AC-6 Feeder System

Cited by 2 publications

References 24 publications

Redefining innate natural antibodies as important contributors to anti-tumor immunity

Redefining innate natural antibodies as important contributors to anti-tumor immunity

A critical role for B cells in cancer immune surveillance

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