Double-negative (CD27−IgD−) B cells are expanded in NSCLC and inversely correlate with affinity-matured B cell populations

Abstract

Background:The presence of B cells in early stage non-small cell lung cancer (NSCLC) is associated with longer survival, however, the role these cells play in the generation and maintenance of anti-tumor immunity is unclear. B cells differentiate into a variety of subsets with differing characteristics and functions. To date, there is limited information on the specific B cell subsets found within NSCLC. To better understand the composition of the B cell populations found in NSCLC we have begun characterizing B cells in lung tumors and have detected a population of B cells that are CD79A . Association of double-negative B cells with clinical data including gender, age, smoking status, tumor diagnosis and pathologic differentiation status were also examined using the logistic regression analysis for age and student's t-test for all other variables. Associations with other B cell subpopulations were examined using Spearman's rank correlation. Results:We observed that double-negative B cells were frequently abundant in lung tumors compared to normal adjacent controls (13 out of 15 cases), and in some cases made up a substantial proportion of the total B cell compartment. The presence of double-negative cells was also found to be inversely related to the presence of affinitymatured B cells within the tumor, Spearman's coefficient of − 0.76. Conclusions:This study is the first to observe the presence of CD27 − IgD − double-negative B cells in human NSCLC and that this population is inversely correlated with traditional affinity-matured B cell populations.

CD11c+ B Cells Are Mainly Memory Cells, Precursors of Antibody Secreting Cells in Healthy Donors

“…The facts that [1] DN cells (CD27 − IgD − ) are atypical memory cells, which are reported to be exhausted, anergic, or preplasma cells. The role of DN cells remains unclear, but it has been observed that DN frequency increases during infection (HIV, malaria, Hantavirus), autoimmune disease (SLE, multiple sclerosis), as well as in non-small cell lung cancer (13,(31)(32)(33)(34)(35). In addition, DN cells are reported to express CD11c in HIV, malaria, Hantavirus infection, SLE, and multiple sclerosis (11,36,37).…”

Th2 Biased Immunity With Altered B Cell Profiles in Circulation of Patients With Sporotrichosis Caused by Sporothrix globosa

“…DN B cells were also found expanded in SLE, HIV and malaria patients, respectively (45)(46)(47), but there is no literature mentioned the relation between DN B cells and T cells till now. Although the origin and function of DN B cells remain unclear, it was suggested that DN B cells may be exhausted memory B cells (48), or precursor memory B cells that have not yet to upregulate CD27 (49), or a product which CD27 fails to upregulate appropriately (50) and the increased DN B cells in SLE patients were considered as precursors of autoantibody producing plasma cells (51). The correlation found in our study implied that DN B cells collaborated with Th2 and Tregs in the immunity against this mycotic infection in human.…”

Interferon-beta treated-multiple sclerosis patients exhibit a decreased ratio between immature/transitional B cell subset and plasmablasts

“…The human memory B-cell compartment is more complex than originally thought based on their antigen-experienced phenotype and differential expression of CD27 and immunoglobulin heavy chain isotypes. Though CD27 is a hallmark of memory B cells, CD27 − memory B cells had been identified, namely CD27 − IgG + and CD27 − IgA + classswitched B cells (Fecteau et al, 2006;Wei et al, 2007;Berkowska et al, 2011;Centuori et al, 2018).…”

“…The CD27 − memory B cell subset has undergone class switching, though they do not gain the expression of CD27. Little is known about the function of these cells in immunity (Centuori et al, 2018). It is therefore tempting to postulate that CD27 − memory cells develop outside the GC in extrafollicular reactions.…”