Venkata A Yeramilli

Loyola University, New Orleans, Louisiana, United States

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Publications (4)16.01 Total impact

  • Venkata A Yeramilli, Katherine L Knight
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    ABSTRACT: In species other than mouse, little is known about the origin and development of marginal zone (MZ) B cells. Using cross-reactive antibodies, we identified and characterized splenic MZ B cells in rabbits as CD27+ CD23- . In rabbits in which organized gut-associated lymphoid tissue (GALT) was surgically removed at birth, we found only CD23+ follicular (FO) B cells and almost no CD27+ MZ B cells in the spleen, indicating that GALT is required for the development of splenic MZ B cells. These findings lead us to suggest that commensal microbiota contribute to the development of MZ B cells.
    European Journal of Immunology 03/2013; · 4.97 Impact Factor
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    Venkata A Yeramilli, Katherine L Knight
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    ABSTRACT: The peripheral B cell compartment in mice and humans is maintained by continuous production of transitional B cells in the bone marrow. In other species, however, including rabbits, B lymphopoiesis in the bone marrow abates early in life, and it is unclear how the peripheral B cell compartment is maintained. We identified transitional B cells in rabbits and classified them into T1 (CD24(high)CD21(low)) and T2 (CD24(high)CD21(+)) B cell subsets. By neutralizing B cell-activating factor in vivo, we found an arrest in peripheral B cell development at the T1 B cell stage. Surprisingly, T1 B cells were present in GALT, blood, and spleen of adult rabbits, long after B lymphopoiesis was arrested. T1 B cells were distinct from their counterparts in other species because they are proliferating and the Ig genes are somatically diversified. We designate these newly described cells as T1d B cells and propose a model in which they develop in GALT, self renew, continuously differentiate into mature B cells, and thereby maintain peripheral B cell homeostasis in adults in the absence of B lymphopoiesis.
    The Journal of Immunology 06/2011; 186(11):6437-44. · 5.52 Impact Factor
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    Venkata A Yeramilli, Katherine L Knight
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    ABSTRACT: The effects of B cell-activating factor belonging to the TNF family (BAFF) on B cell maturation and survival in the mouse are relatively well understood. In contrast, little is known about the role of BAFF in B cell development in other mammals, such as rabbits, that use GALT to develop and maintain the B cell compartment. We examined the expression and requirement of BAFF and a proliferation-inducing ligand (APRIL) during peripheral B cell development in young rabbits. By neutralizing BAFF and APRIL in neonates with a soluble decoy receptor, transmembrane activator calcium modulator and cyclophilin ligand interactor-Fc, we found a marked reduction in the number of peripheral B cells, but found no change in the bone marrow (BM) compartment. In the appendix, the size and number of proliferating B cell follicles were greatly reduced, demonstrating that although BAFF/APRIL is dispensable for B cell development in BM, it is required for B cell development in GALT. We found that all rabbit B cells expressed BAFF receptor 3, but did not bind rBAFF, suggesting that the BAFF-binding receptors (BBRs) are bound by endogenous soluble BAFF. Further, we found that B cells themselves express BAFF, suggesting that the soluble BAFF bound to BBRs may be endogenously produced and stimulate B cells in an autocrine fashion. Additionally, we propose that this chronic occupancy of BBRs on B cells may provide a tonic and/or survival signal for the maintenance of peripheral B cells in adults after B lymphopoiesis is arrested in BM.
    The Journal of Immunology 05/2010; 184(10):5527-36. · 5.52 Impact Factor
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    Venkata Arunachalam Yeramilli
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    ABSTRACT: In rabbits, the primary antibody repertoire is generated in the gut-associated lymphoid tissues (GALT), where bone marrow (BM)-derived B cells undergo a proliferative expansion and somatically diversify the immunoglobulin genes. Unlike in other species, B lymphopoiesis in rabbit arrests a few months after birth, and it is unclear how the peripheral B cell compartment is maintained when there is no influx of newly-made B cells from the BM. For my dissertation, I investigated how B cells develop in the GALT of rabbits, and how they are maintained in adults after the arrest of lymphopoiesis. To identify cellular signals that promote B cell expansion in GALT, I introduced soluble decoy receptors into newborn rabbits and found that B cells in GALT expand in a B7-CD28 independent, CD40-CD40L, CR2-CR2L, and BAFF-BAFF-R dependent manner. Using several cross-reactive antibodies, I identified subpopulations of transitional (T1 and T2) B cells in the peripheral tissues of both young and adult rabbits. Unlike in other species, T1 B cells in rabbit were proliferating and were somatically diversified, suggesting that these B cells are not newly-made, but somehow maintained in the periphery of adults. Further, unlike in other species, I found that recombinant BAFF did not bind to primary B cells, and I demonstrated that this lack of binding was due to occupied BAFF-binding receptors. Taken together, my work provides some insights into how B cells develop and are maintained in adult rabbits. My work suggests that B cells in GALT develop in a T cell- independent and BAFF and complement-dependent manner. In adults, I designate the somatically diversified transitional B cells as T1d B cells and propose that they are maintained by self-renewal. I propose a model for peripheral B cell homeostasis in adults, wherein self-renewing T1d B cells continuously differentiate into mature B cells. Additionally, I propose that the chronic occupancy of BBRs on primary B cells with endogenous BAFF, provides B cells with a tonic/survival signal, and consequently allows them to remain long-lived.
    01/2010;

Publication Stats

14 Citations
16.01 Total Impact Points

Institutions

  • 2013
    • Loyola University
      New Orleans, Louisiana, United States
  • 2010–2013
    • Loyola University Chicago
      • Department of Microbiology and Immunology
      Chicago, IL, United States