Modulation of Igβ is essential for the B cell selection in germinal center

Abstract

The positive and negative selection of antigen-reactive B cells take place in the germinal center (GC) during an immune responses. However, the precise molecular mechanisms underlying these selection machineries, including the involvement of antigen receptor signaling molecules, remain to be elucidated. We found that expression levels of Igα and Igβ, which are the essential components of B cell antigen-receptor complex, were differentially regulated in GC B cells and that the expression of Igβ was more prominently down-regulated in a portion of GC B cells. The suppression of Igβ down-regulation reduced the number of GL7+GC B cells and the affinity maturation in T-dependent responses was markedly impaired. In addition, the disease phenotypes in autoimmune-prone mice were ameliorated by blocking of Igβ down-regulation. These results suggest that Igβ down-regulation is involved in the normal positive selection in GC and the accumulation of autoreactive B cells in autoimmune-prone mice.

Presence of Natural Killer B Cells in Simian Immunodeficiency Virus-Infected Colon That Have Properties and Functions Similar to Those of Natural Killer Cells and B Cells but Are a Distinct Cell Population

“…This may not be surprising given that affinity maturation occurs in the germinal centers of secondary follicles of lymphoid tissues. Downmodulation of CD79b is essential for B-cell selection in the germinal center ( 52 ) and possibly antigen presentation to T follicular helper cells ( 53 ). This may not be the case for NKB cells.…”

“…We support this by finding that CD79b is not found within NK cells from SIV-infected colons, even though intracellular IgM is present there (data not shown). Unlike IgA-bearing B cells with downmodulated CD79b, IgM-bearing B cells express CD79b ( 52 ). Thus, more studies are needed to determine the mechanism leading to Ig expression in NK and NKB cells in the infected colon to determine whether NKB cells arise from pro-B or NK cells.…”

Tonic B-cell receptor signaling in diffuse large B-cell lymphoma

“…GCB-DLBCL was named for similarity to centroblasts of the germinal center, which functions to select B-cell clones with high BCR affinity to antigen, a process involving upregulation of BCR surface levels. 52,53 The type of BCR signaling (tonic, antigen-induced, or both) enhanced by higher BCR levels in centroblasts is unknown, but the 2 types may be somewhat merged in GC B cells, whose response to BCR ligation, as compared with that of non-GC mouse B cells, is less activating of NF-kB. 54 Our results from CD79A modification are consistent with those in mouse B cells bearing CD79A-modified complete BCR complexes, [27][28][29] or artificial proteins containing CD79A and/or CD79B cytoplasmic tails (which can drive the development of follicular B cells in BCRdeficient mice), 55,56 but differ in identifying Y188 as the ITAM tyrosine most involved in tonic BCR signaling.…”

Continuous signaling of CD 79b and CD 19 is required for the fitness of Burkitt lymphoma B cells

“…That only Igβ but not Igα has a special B‐cell survival function is also suggested by a study in mice with an inducible deletion of either the Igβ or Igα tail (Song et al , 2016). Interestingly, the expression of Igβ is specifically down‐regulated in germinal center B cells, suggesting that during the selection for high‐affinity B‐cell clones, the Igβ/CD19 signaling module is switched off (Todo et al , 2015). …”