The continuing story of T-cell independent antibodies

The purpose of this article is to review the role of extrafollicular and T-cell independent antibody responses in humoral immunity. We consider two interrelated questions: (a) do T-cell independent antibody responses dominated by IgM and/or IgA play unique functions in immunity and homeostasis; and (b) is it typical for these responses to result in lifelong protection? In addressing these questions, we consider the established advantages of T-cell driven responses including the unique role played by germinal center reactions in these responses, and contrast the processes and outcomes of germinal center-centric responses with germinal center- and T-cell independent antibodies. We suggest that T-independent and other extrafollicular responses contribute substantially to highly stable antibody repertoires in both the serum and the intestine, providing relatively constitutive humoral barriers with the collective dual function of protecting against invading pathogens and regulating the composition of non-pathogenic microbial communities.