Group 2 Innate Lymphoid Cells Promote an Early Antibody Response to a Respiratory Antigen in Mice

Abstract

Innate lymphoid cells (ILCs) are a new family of immune cells that play important roles in innate immunity in mucosal tissues, and in the maintenance of tissue and metabolic homeostasis. Recently, group 2 ILCs (ILC2s) were found to promote the development and effector functions of Th2-type CD4+ T cells by interacting directly with T cells or by activating DCs, suggesting a role for ILC2s in regulating adaptive immunity. However, our current knowledge on the role of ILCs in humoral immunity is limited. In this study, we found that ILC2s isolated from the lungs of naïve BALB/c mice enhanced the proliferation of B1- as well as B2-type B cells and promoted the production of IgM, IgG1, IgA, and IgE by these cells in vitro. Soluble factor(s) secreted by ILC2s were sufficient to enhance B cell Ig production. By using blocking antibodies and ILC2s isolated from IL-5-deficient mice, we found that ILC2-derived IL-5 is critically involved in the enhanced production of IgM. Furthermore, when adoptively transferred to Il7r−/− mice, which lack ILC2s and mature T cells, lung ILC2s promoted the production of IgM antibodies to a polysaccharide antigen, 4-hydroxy-3-nitrophenylacetyl Ficoll, within 7 days of airway exposure in vivo. These findings add to the growing body of literature regarding the regulatory functions of ILCs in adaptive immunity, and suggest that lung ILC2s promote the B cell production of early antibodies to a respiratory antigen even in the absence of T cells.

IL‐33: biological properties, functions, and roles in airway disease

“…The adoptive transfer of both ILC2s and CD4 + T cells, but not each cell population alone, into IL‐7R‐deficient mice that lacked both ILC2s and CD4 + T cells, induced a robust airway inflammation and antigen‐specific type 2 immune responses . Furthermore, IL‐33‐activated ILC2s enhanced B‐cell proliferation and promoted antibody production, including IgM, IgG1, IgA, and IgE, in vitro . Consistent with these data, the papain‐induced IgE response was attenuated in ILC2‐deficient mice …”

Innate lymphoid cells and allergic disease

“…4 Co-culture of ILC2 with B1 or B2-type B cells enhanced B cell proliferation and antibody production, and adoptive transfer of ILC2 into Il7r −/− mice enhanced B1 cell antigen-specific IgM production. 95 Consistent with these findings, ILC2 promote IgA expression and self-renewal in B1 cells, likely via IL-5 and/or IL-6 expression. 5 ILC2 also have the capacity to produce IL-4, and this may shape B cell class switching.…”

Type 2 innate lymphoid cells in the induction and resolution of tissue inflammation

“…Along with regulating effector and regulatory T cells, ILC2s can also promote B cell responses. ILC2s stimulated B1 cell proliferation in an IL‐5‐dependent manner in vitro and in vivo . In addition, B cells activated with IL‐4 and either anti‐CD40 or LPS produced more IgM, IgG1, IgE, and IgA if they were cultured in the presence of ILC2s .…”