Transitional B Cells: How Well Are the Checkpoints for Specificity Understood?

Abstract

It is crucial for the immune system to minimise the number of circulating mature self-reactive B cells, in order to reduce the potential for the development of autoantibody-related autoimmune diseases. Studies of animal models have identified two major checkpoints that ensure that such cells do not contribute to the naïve B cell repertoire. The first is in the bone marrow as B cells develop and the second is in the spleen; B cells that are released from the bone marrow as transitional B cells go through more stringent selection in the spleen before they develop into mature naïve B cells. Transitional B cells and their maturation have mostly been studied in mice. However, recent studies characterised human transitional B cells and found considerable differences to current models. In this review, we will consider these differences alongside known differences in mouse and human splenic function and ask whether human transitional B cells might develop along a different pathway.

Transitional B cell subsets in human bone marrow

“…Interestingly, CD5 was not expressed uniformly on BM transitional B cells, as was expected in light of current definitions of transitional cells in human PB [22,23]. A significantly greater proportion of T2 B cells expressed CD5 compared to T1 B cells (Fig.…”

Antibody-Dependent Cell-Mediated Cytotoxicity Epitopes on the Hemagglutinin Head Region of Pandemic H1N1 Influenza Virus Play Detrimental Roles in H1N1-Infected Mice

“…Experimental mouse models are an invaluable scientific resource that allow comprehensive investigation of key biological questions in vivo and provide an essential platform in the study of many human diseases. It has been widely acknowledged that the mouse and human antibody repertoire share a general similarity (34)(35)(36). However, differences in germline antibody repertoire exist between species, and the number of mature naïve B cells from mice is smaller than that from humans (37).…”

A role for gut-associated lymphoid tissue in shaping the human B cell repertoire

“…Both are mature naive populations; the former generate conventional adaptive T cell-dependent B cell responses, whereas the latter are responsible for more innate type responses to T-independent antigens such as pneumococcal polysaccharide. This is unlikely to occur equivalently in humans where splenic zonal microanatomy is different (Mebius and Kraal, 2005;Vossenkämper and Spencer, 2011) and where there are fundamental differences in B cell subset biology. For example, mice have a self-renewing peritoneal B1 B cell population that humans do not have equivalently.…”